1. health and fitness
2. disease

Technical Information
International Edition
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Coccidiocide for Lambs
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Contents
Introduction .................................................................................. 4
Coccidiosis in Sheep .................................................................... 6
Morphology of Eimeria spp. in Sheep ................................................. 6
Life Cycle of Ovine Coccidia ............................................................. 7
Prevalence and Epidemiology .......................................................... 10
Clinical and Pathological Manifestations ........................................... 14
Diagnosis ...................................................................................... 21
Management and Control ............................................................... 33
Baycox® 5% (Toltrazuril) ............................................................... 36
- Active Ingredient ................................................................. 36
- Spectrum of Activity ............................................................. 37
- Mode of Action ................................................................... 37
- Pharmacokinetics ................................................................ 37
- Treatment Time .................................................................... 38
Efficacy Trials ................................................................................ 41
References ................................................................................. 48
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Introduction
Coccidiosis is a disease of the
intestinal tract of sheep caused by
protozoa parasite Eimeria sp.
Coccidiosis is usually insidious and
the disease only becomes evident in
infected animals after they show
clinical signs such as diarrhoea,
debilitation, or refusal of feed.
Following the ingestion of sporulated
coccidia oocysts from a
contaminated environment, the
parasite attaches to the epithelial
lining of the intestines, invades and
multiplies in the intestinal cells. After
the pre-patent period of 12 – 20
days depending on the Eimeria
species involved and its
patogenicity, sheep start shedding
oocysts in the faeces and
contaminating the environment.
Sheep coccidiosis has greatest
impact on lambs less than 3 month
old, causing severe damage to the
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intestinal tract. It is associated with
diarrhoea, dehydration, impared
weight gain, or weight loss and
death in some cases (Helle, 1970;
Gjerde and Helle, 1991;
Reeg et al., 2005). The economic
impact of coccidiosis was calculated
in small ruminants by Fitzgerald in
1980, at around US $ 140 million
annually worldwide.
Bayer Animal Health has more than
40 years experience in the control of
coccidiosis. Numerous studies have
been conducted and published by
Bayer Animal Health about the
epidemiology and control of
coccidiosis in different animal
species. Baycox® 5% oral
suspension has been developed by
Bayer Animal Health for the control
of coccidiosis in sheep as a single
one-dose ready to use product.
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Coccidiosis in Sheep
Morphology of Eimeria spp. in Sheep
Sheep coccidiosis is caused by protozoan parasites of the genus Eimeria. The
morphological characteristics of sheep Eimeria spp. are detailed in table 1. It is
reported from many countries around the world. Fifteen Eimeria spp. were described
as etiological agents in sheep (Reeg et al., 2005, Rommel 2000) and 10 species
have been found in central Europe (Reeg et al., 2005). In Central and Eastern
Europe, Eimeria ovinoidalis, Eimeria bakuensis, Eimerai crandallis/Eimeria
weybridgensis, Eimeria parva and Eimeria faurei are the predominant species
(Rommel 2000). Two of the 15 species that infect sheep, Eimeria crandallis and
Eimeria ovinoidalis, have been associated with the disease in lambs, and they
are considered to be the most pathogenic Eimeria species for sheep.
Table 1. Morphological Characteristics of Eimeria species in Sheep
Eimeria
species
Size (µm)
Shape
Color
oocyst
Oocyst
polar cap
Pathogenicity
Oocyst
residium
Sporocyst
residium
Sporulation
time (days) at
20 ºC
E. ahsata
29-44 x 17-28
Ovoid
yellowish
+
++
-
+
2-3
E. bakuensis
23-36 x 15-24 Elongante to
ellipsoidal,
often parallel
or straight
oocyst wall
yellowish
+
++
-
+
2-4
E. crandallis
17-28 x 17-22
Broad
ellipsoidal to
spherical
colourless
+/-
+/++
-
+
1 -3
E. granulose
22-37 x 17-26 Urn-shaped,
ovoid
yellowish
+
-
-
+
3-4
E. intricata
40-56 x 30-41
Ellipsoidal
Brown
+
-
-
+
3-7
E. marsica
15-22 x 11-14
Ellipsoidal
colourless
+
-
-
+
3
E. punctata
18-28 x 16-21
Ovoid
-
+
-
+
+
2
Broad
ellipsoidal to
spherical
colourless
+
-
-
+
1 -3
25-37 x 19-27
Oval to
pyriform
Pale,
yellowishbrown to
greenish
-
-/+
-
-
1 -3
E. ovinoidalis 17-28 x 12-23
Oval to
ellipsoid
Colourless
to pale
yellowish
-
+++
-
+
1 -3
E.
17-31 x 14-19
weybridgensis
E. faurei
E. pallida
12-20 x 8-15
Ellipsoidal,
delicate wall
colourless
-
-
-
+
1 -3
E. parva
10-22 x 10-19
Spherical to
subspherical
colourless
-
+ / ++
-
+
3-5
Provided by Department of parasitology, faculty of veterinary medicine, University of Leipzig, Germany
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Life cycle of ovine coccidia
All Eimeria species are monoxenous.
Infection of an animal occurs following
the ingestion of water or feed contaminated with sporulated oocysts. The life
cycle of coccidia has two phases: an
exogenous phase and an endogenous
phase (Fig 1). The exogenous phase
takes place outside of the body in the
environment and is called “sporulation
of oocysts“. During the endogenous
phase, which occurs internally, the
parasite undergoes numerous divisions
in the intestinal cells. Both stages are
described below.
Figure 1. Life cycle of ovine coccidia
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Exogenous phase
Endogenous phase
The unsporulated oocysts are
passed out in the faecal material of
the sheep into the environment.
Under optimal environmental
conditions such as moisture,
temperature (24 – 32°C) and
oxygen, unsporulated oocysts of
most species sporulate in approximately 2 to 5 days. Oocysts are
usually killed at temperatures over
40°C and below -30°C, but
between these extremes, sporulated
and non sporulated oocysts can
remain viable for more than a year
(Foreyt, 1986). Unsporulated
oocysts are more susceptible to
extreme changes in climatic
conditions than sporulated oocysts.
(Horton-Smith and Long, 1954).
Oocysts can withstand freezing at
-5°C to -8°C for several months
(Schneider et al., 1972) and have
been shown to be able to overwinter in Norway on pastures and be
infective to grazing animals in the
next grazing season (Helle, 1970).
The sheep ingests up the sporulated
oocysts with contaminated feed or
water. Once into the digestive tract,
the digestive tract enzymes exert
their influence on the oocysts
weakening the oocyst wall sufficiently so that the active sporozoites
escape into the lumen of the gut
(Fitzgerald, 1980). These sporozoites enter the appropriate host
mucosal cells. At this stage the
sporozoites are called trophozoites.
They then undergo nuclear division,
or schizogony, and schizonts are
formed. This is the first generation of
schizogony.
The endogenous phase of the life
cycle starts after uptake of the
sporulated oocysts.
When the schizonts mature, the
first-generation of merozoites is
released and they enter other
appropriate host cells and continue
the cycle of asexual development. In
the new host cell the merozoites
round up to become trophozoites
and undergo nuclear fission or
asexual division as before, developing into second-generation schizonts and, in turn, into second-generation merozoites.
Second-generation merozoites may
develop further into subsequent
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generations of merozoites. This
asexual reproduction, however,
does not continue indefinitely.
The number of merozoite generations (asexual multiplication generations) varies between two and more
from species to species. After a
fixed number of schizogony (merozoite generations), the last generation merozoites begin the sexual
reproduction phase (gametogony).
The last-generation merozoites
change into trophozoites that,
instead of repeating schizogony,
differentiate into macrogametocytes
(macrogamonts) and microgametocytes (microgamonts). These grow to
full size and each macrogametocyte
gives rise to one macrogamete.
Each microgametocyte gives rise to
a large number of biflagellate
microgametes.
Fertilization of the macrogamete by
the microgamete results in the
formation of a zygote. The zygote
lays a wall around itself to form an
oocyst. The oocyst breaks out of the
host cell into the intestinal lumen
and is excreted with faeces.
The prepatent period (the time taken
oral uptake of sporulated oocysts to
excretion of oocyst) is 15-20 days
for Eimeria crandallis, and 12-15
days for Eimeria ovinoidalis.
The young microgametes contain
small granules in the vicinity of
nucleus, which later enlarge and
scatter over the cytoplasm. The large
granules are found on the periphery
of the cell and are called “wallforming granules” that form the wall
of the oocyst after fertilization of the
macrogamete.
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Prevalence and epidemiology
Prevalence
Ovine coccidiosis is present worldwide in almost all sheep rearing
countries (Pellerdy, 1974) and it is
assumed that most, if not all,
domestic ruminants become infected
with coccidia during their lives
(Taylor and Catchpole, 1994).
However some Eimeria species are
more important than others with
regard to their pathogenicity.
Amongst various ovine coccidia
species, Eimeria crandallis and
Eimeria ovinoidalis are important
from a clinical point of view. In
central Europe, 10 Eimeria species
have been found (Reeg et al., 2005).
The prevalence of coccidiosis in
different countries is summarized in
table 2.
Table 2. Prevalence of sheep coccidiosis in different countries
Country
Germany
Turkey
E. crandallis
E. ovinoidalis
Eimeria sp.
No. of animals
(flocks)
Reference
-
-
43.1%
524
Epe et al. 2004
100 %
100 %
-
222
Reeg et al. 2005
98.2-100 %
96.5-100 %
26.3-100%
239
Barutzki et al. 1990
64.9 %
35.2 %
13.7 %
55.24%
43.5 %
47.7 %
97.9 %
248
241
592
Kaya 2004
Gül 2007
Arslan et al. 1999
Switzerland
-
-
97.5 %
122
Pfister and Flury 1985
Hungary
8.6 %
51.5 %
-
(15)
Hovarti and Varga, 1986
Poland
-
-
4.6-60 %
-
Gorski et al. 2004
-
-
20.7-8.5%
1740
Nowosad et al. 2002
New Zealand
70 %
-
93 %
215
McKenna 1972
Austria
27.3 %
28.3 %
97-100 %
186
Platzer et al. 2005
Czech Repub.
-
-
67-88 %
(4)
Jelonova et al. 1990
-
-
74-98 %
50 - 70
Chroust et al. 1998
USA
85 %
-
100 %
219
Ajayi and Todd, 1977
Spain (Mallorca)
-
-
75.1%
197
Gomez et al. 1998
UK
72.5 – 86.1 %
9.7 - 36.2 %
-
135
Berriatua et al. 1994
Mexico
-
-
81.7 %
(15)
Nahed-Toral et al. 2003
Italy
-
-
95.3 %
160
Ambrosi et al. 1982
-
-
47.7 %
65.6 %
(904) adult
(375), young
Arru et al. 1984
Brazil
47.2%
52.8%
-
30
Silva et al. 2008
France
6–8%
32 – 35 %
80 – 100 %
-
Mage et al 1995
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Epidemiology
Coccidiosis is a frequently
diagnosed, but often misunderstood
and neglected parasitic infection
in sheep. Outbreaks of disease are
known to occur from the tropics
to the temperate zones, but little
is known of the significance of
coccidial infections in arctic zones
(Fitzgerald, 1980). Since sporulated
oocysts are the infective stage of the
pathogen, the sporulation of oocysts
excreted via feces in the environment
is crucial. Sporulation of Eimeria
species in general is most rapid at
28°C to 31°C. Low temperatures
of 0°C to 5°C retard sporulation,
but sporulation will occur when the
temperature is increased. Species
of ovine coccidia can survive for 7
days at -25°C. Storage of Eimeria
oocysts at 4°C for 14 weeks reduced
sporulation by approximately 50
percent, whereas storage at 4°C for
26 weeks prevented sporulation
(Foreyt, 1986). There is some
evidence that some oocysts survive
the winter in most areas of the US
and lambs become infected in spring
when they ingest the oocysts (Foreyt,
1986). Coccidiosis affects mostly
young animals. Taylor and Catchpole
(1994) pointed out that coccidiosis
is most commonly seen in unweaned
lambs aged 4-7 weeks either indoors
or on heavily-stocked pasture in
cold wet weather. Similarly, Foreyt
(1986) stated that clinical coccidiosis
is observed most frequently in 2
to 8 week-old lambs housed with
their dams; in lamb rearing facilities; in lambs 2 to 3 weeks after
weaning that are entering feedlots
or experiencing a change in diet; or
after severe periods of stress, such as
shipping, bad weather, or concomitant disease. The disease may also
occur in ewes and lambs that are
maintained for long periods of time
on contaminated wet areas or heavily stocked irrigated pastures. The
susceptibility of lambs to coccidiosis
increases with the age up until about
4 weeks. But, young lambs are most
susceptible to coccidiosis. In France
(Yvore and Esnault, 1987) and
Ireland (Taylor and Kenny, 1988),
coccidiosis is seen after weaning,
or after changes in nutrition or
environment. Orgeur et al. (1998)
studied the consequences of 2
different type of weaning regimes,
progressive weaning (PROG) and
sudden weaning (SUDD), and found
out that in lambs the number of
oocysts excreted at 9.5 and 16.5
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weeks of age was higher in PROG
than in SUDD lambs. In the USA,
coccidiosis causes problems in
feedlot lambs which are weaned
and transported often over long
distances and kept crowded together
(Mahrt and Sherrick, 1965). Bauer
(1989) reported that an outbreak of
eimeriosis in suckling lambs occurred
two weeks after turn-out on pasture
and in the same flock Nematodirus
battus infection was detected for the
first time in Germany. Barutzki et al.
(1989) found a relation between age
and season concerning the oocyst
output in lambs in Germany. In this
epidemiological study it was shown
that the intensity and persistence of
oocyst output showed distinct age related differences, since lambs always
passed oocysts in larger numbers
and more frequently than either ewes
or yearlings. The total oocyst output
in lambs reached a peak in March/
April. E. bakuensis, E. ovinoidalis,
E. parva, E. weybridgensis/
crandallis were regularly isolated
and were associated with a high
faecal OPG (oocysts per gram
faeces) value. In the UK, E. crandallis
and E. ovinoidalis were the predominant species found in 5-6 weekold lambs with diarrhea and a
high faecal OPG of 105 (Gregory
et al. 1980). In this study, most of
the faecal samples showed three
or more coccidial species present.
Same authors published in 1989 that
management at lambing plays a role
in the epidemiology of ovine coccidiosis. Of 24 lambing pens, 12 were
left unused until halfway through the
lambing period. The others were
used normally, with a record kept
of the occupants and of their faecal
oocyst output. The mean daily weight
gain up to 10 weeks of 22 lambs in
used pens was 38 per cent greater
than that of the 18 lambs in unused
pens. They were also heavier at
weaning. Authors suggested that an
early challenge with coccidia, before
the lamb becomes susceptible to
their pathogenic effect, may help to
reduce clinical coccidiosis (Gregory
et al. 1989). Factors which play
important role in the epidemiology of
coccidiosis were presented in figure 2.
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Host
• Susceptibility/age
• Stress factors
(change of diet, weaning,
shipping, crowding etc.)
• Immune status
• Exposure
Parasite
• Number
• Type
• Dispersion
Environment
• Conditions for sporulation
(temperature, oxygen, humidity)
• Management system (loose bedding,
slatted flooring, pasture etc.)
• Hygiene
• Feed hygiene, Drinking hygiene
• Climate
Fig 2. Factors participating in the epidemiology of coccidiosis
Taylor (1995) reported that ewes are
often considered to be the source
of infection for lambs and initially
this may be true. If infected soon
after birth, a lamb`s first encounter
with coccidian usually causes no
disease. However, coccidian can
still establish themselves and multiply
enormously meaning that if a lamb
picks up a few thousand oocysts
during its first week of the life it will
release several thousand million
into the environment two to three
weeks later. Hidalgo-Agüello and
Cordero-Del-Campillo (1987) found
a relationship between season/age
and oocyst excretion in Spain.
Geographical and climatic
conditions in different regions of
Spain influenced the infection level
in sheep and the highest oocyst
excretion rate was found in the
lambs. A significant difference was
observed between different age
groups. In France according to Le
Sueur et al. 2007, in sheep-pen
lambs, infection occurs generally
during the days following birth and
the majority of the lambs exhibit
signs of coccidiosis between
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4 & 7 weeks of age. In France, the
3 major risk periods are the days
following birth, weaning and after
the grazing season. The major
pathogenic Eimeria species in French
sheep are Eimeria ovinoidalis,
Eimeria ovina and Eimeria crandallis (Mage, 1995). In the
figure 3, the oocysts shedding
period just after lambing in French
intensive sheep rearing farm was
presented (Le Sueur et al. 2007).
Figure 3. Percentage of lambs with positive OPG after lambing in an intensive sheep rearing farm
in France (Le Sueur et al. 2007, unpublished)
Clinical and pathological
manifestations
E. crandallis and E. ovinoidalis
are the most pathogenic Eimeria
species in sheep. E. bakuensis and
E. parva are also considered to
have some degree of pathogenicity
in sheep (see table 1). However,
in most cases coccidiosis occurs as
a result of mixed infection and it is
very rare for it to be caused by one
single species only. In table 3 and
4 the sites of infection and prepatent periods are listed. Coccidiosis
is normally a flock problem. The
first sign that coccidiosis may be
affecting a flock is that lambs may
not be thriving as well as expected.
Several lambs may have a
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tucked-up and open fleeced appearance with a few showing faecal
staining around the rear end due to
diarrhea. Lambs eventually lose their
appetite and become weak und unthrifty (Taylor, 1995). The severity of
damage to the intestinal mucosa is
closely associated with the number
of pathogenic species’ oocysts
picked up from the environment. As
the disease progresses, some lambs
show profuse watery diarrhoea,
often containing streaks of blood.
If left untreated, these animals may
continue to scour and eventually
die of dehydration (Taylor, 1995).
Affected animals are depressed and
anorectic (Foreyt, 1986). In the
figure 4, a typical sign of diarrhea
in lambs and in the figure 5
retarded growth of a lamb due to
coccidiosis was presented.
Figure 4. Diarrhoea due to coccidiosis in sheep (both left and right)
Figure 5. Left: lamb suffered from coccidiosis
(retarded growth)
Right: lamb with normal growth.
Typical signs of clinical coccidiosis
in lambs are (Taylor, 1995):
• Diarrhoea
(with or without mucus or blood)
• Fever
• Inappetance
• Abdominal pain
• Unthriftiness and weight loss
• Anaemia
• Fleece damage
• Death
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Table 3. Site of infection and prepatent period of Eimeria spp. in sheep
Eimeria sp.
Infection site (Taylor 1995)
Prepatent period (days)
(Taylor et al. 2007)
E. ovinoidalis
Ileum and caecum, colon
12 - 15
E. crandallis
Ileum and caecum, colon
15 - 20
E. bakuensis
Small intestine
18 - 29
E. ahsata
Small intestine
18 - 30
E. faurei
Small and large intestine
13 - 15
E. intrica
Small intestine
23- 27
E. parva
Small intestine
12 -14
E. weybridgensis
Small intestine
23 -33
Table 4. Site of infection and prepatent period of Eimeria spp. in goats
(Taylor et al. 2007).
Eimeria sp.
IInfection site
E. alijevi
Small and large intestine
Prepatent period (days)
7-12
E. aspheronica
Unknown
14-17
E. arloingi
Small intestine
14-17
E. caprina
Small and large intestine
17-20
E. caprovina
Unknown
14-20
E. christenseni
Small intestine
14-23
E. hirci
Unknown
13-16
E. jolchijevi
Unknown
14-17
E. ninakohlyakimovae
Small and large intestine
10-13
E. ovinoidalis is seen as the most
pathogenic species occurring in
sheep. Affected animals show
diarrhoea, which is usually
hemorrhagic, abdominal pain
and anorexia. On postmortem the
caecum is usually inflamed, empty
and contracted and the caecal wall
is hyperemic, oedematous and
thickened. In some cases the
mucosa may be hemorrhagic. Ileum
and colon may also be affected.
Much of the damage to the caecum
is associated with the gamonts
because they are the most numerous
(Taylor and Catchpole, 1994).
Mucosal polyps in sheep due to
coccidiosis caused by Eimeria
bakuensis were presented in the
figures 6 and 7.
Tontis and Häfeli (1985) reported
that they observed multiple polyps
in the small intestines of small
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Figure 6. Mucosal polyps in jejunum (3 – 8 mm)
caused by E. bakuensis (Takla, 1992)
Figure 7. Eimeria bakuensis polyps in small
intestine
(Crown copyright - picture supplied by Prof Mike Taylor)
ruminants caused by coccidiosis. In
lambs polyps were located in the
jejunum and ileum and 2/3 of the
intestines were affected by polyps
at a rate of 3 to 12 polyps in 10
cm of intestine. Authors related
this finding to chronic coccidiosis
in lambs. Gregory et al. (1987)
reported that E. crandallis and E.
bakuensis can stimulate host-cell
mitosis and also that they may be
able to synchronize their division
with that of the host cells. In Eimeria
crandallis Infection and in coccidial
polyps, the parasites can divide
continuously in synchrony with the
host epithelial cells, thereby
prolonging endogenous
multiplication for an indefinite
number of generations. This
process can explain the
development of intestinal
polyps observed in lambs
affected by coccidiosis.
A total number of 21 small
ruminants including six goats and
15 sheep aged between 2 weeks
and 6 years old with histories of
depression, loss of appetite, yellow
to dark watery diarrhea, progressive
dehydration and emaciation were
referred for diagnosis of coccidiosis
(Tafti and Mansourran, 2008). At
necropsy, gross lesions were seen
mostly in the jejunum, ileum, cecum,
and sometimes in the proximal
colon. Three cases had minimal
lesions including a few scattered,
whitish, non-pedunculated to
pedunculated nodules on the
mucosa of the jejunum and ileum.
Eighteen cases had marked lesions
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including numerous small whitish
non-pedunculated nodules on the
mucosa of the jejunum, ileum, cecum,
and proximal colon. Advanced cases
had adenomatous-like mucosa and a
cerebriform or gyrate pattern on the
serosal surface. The most common
lesions were in the jejunum, ileum,
and cecum, observed grossly as
non-pedunculated whitish nodules and
microscopically, as proliferative enteritis
with presence of developmental stages
of the Eimeria in the hyperplastic
enterocytes (Tafti and Mansourian
2008).
In an experimental study, Gregory et al.
(1987) observed that in lambs infected
with 5 x 104 or more oocysts and killed
before day 14 after inoculation, giant
meronts were seen in the small intestine
as pin-point white spots visible to the
naked eye. Crypt hyperplasia
(increased length of crypts) and
atrophy (shortening of villi) were seen
to varying extents at all stages. Doses
higher than 106 caused extensive loss
of epithelial cells in the lower jejunum
both from the surface and from the
crypts at 10 days post inoculation
when the first generation of meronts
were mature. Doses of 103 oocysts
or more caused diarrhea from about
13 day post inoculation in both first
and second infections, which was
associated with massive invasion of the
caecal epithelium by second-generation
meronts and gamonts.
In an other experimental study, Gregory
and Catchpole (1990) infected lambs
aged between 4 and 12 weeks of
age with doses of sporulated oocysts
of Eimeria crandallis ranging from
50 to 300.000.000. Clinical effects
were very variable and not closely
related to the inoculating dose. Some
lambs showed intermittent diarrhea,
sometimes watery and sometimes
containing muco-fibrinous material,
either in the form of intestinal casts or
as grayish discoloration. Loss of surface
epithelial cells and villous atrophy in the
small intestine due to the first generation
of meronts and severe diffuse crypt
Figure 8. Massive infiltration of macro and
microgamots and oocysts into epithelia in a
lamb (Takla, 1992).
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hyperplasia in the small and large
intestine due to pro-gamonts were
observed in histopathological
examinations. Massive infiltration of
macro and microgamots and oocysts
into epithelia of the intestine in a lamb
were reported by Takla (1992) and
presented in the figure 8. Giant meronts
in the large intestinal mucosa due to
Eimeria ovinoidalis to be seen in the
figure 9.
the inoculum. Even 1000 oocysts
of each species caused diarrhea.
The pathogenic effect was attributed
mainly E. ovinoidalis. Hemorrhagic
intestines due to Eimeria ovinoidalis
coccidiosis in sheep were presented
in the figure 10.
Figure 10. Hemorrhagic intestines due to
E. ovinoidalis. Caecum of a lamb that died of
coccidiosis (Crown copyright – picture supplied
by Prof Mike Taylor)
Figure 9. Eimeria ovinoidalis. Large intestinal
mucosa with giant meronts (Crown
copyright – picture supplied by Prof Mike Taylor)
In an experimental study of Gregory et al. (1989), no pathogenic
effect was detected in lambs when
104 oocysts of each species E.
crandallis and E. ovinoidalis were
inoculated before 72 h of age.
However at 4 weeks of age the
combined inoculum caused diarrhea
and weight loss, the severity being
roughly proportional to the size of
Coccidiosis impacts the weight gain
of lambs as in other animals. Effect of
different doses of sporulated oocysts
of E. crandallis and E. ovinoidalis on
weight gain in lamb was studied by
Gregory et al. (1989) and presented
in figure 11.
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Body weight AS¬% of weight of inoculation
140
500
135
130
1000
125
5 000
120
10 000
115
15 000
110
One lamb died
105
100
0
6
14
16
19
Days after inoculation
(Gregory et al. 1989)
Figure 11. Body weight of lambs (as % of weight on inoculation) inoculated at about 5 weeks
of age with different doses of oocysts of both Eimeria crandallis and Eimeria ovinoidalis
(Gregory et al. 1989).
Figure 12. Pasty faeces from a lamb with
coccidiosis
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Diagnosis
A: Diagnostic methods
Faeces samples from lambs (pasty
(Figure 12) or watery) can be taken
directly from rectum.
Most of the ovine Eimeria spp. can
be differentiated by an experienced
examiner by the morphology of the
unsporulated oocysts. For the
species E. crandallis and
E. weybridgensis this is not possible
and therefore they are differentiated
by the shape and position of the
sporocysts and sporozoites.
Additionally E. parva and E. pallida
are difficult to separate from each
other because of their similarity and
therefore sporulated oocysts can be
helpful.
a) Sporulation of faeces
• Weigh 4 g of faeces in a petri
dish, flatten it and add 2%
potassium dichromate solution
(K2Cr2O7) to avoid overgrowth
with fungi and bacteria
• Store the samples at room temperature with daily aeration, because oxygen is necessary for
sporulation of oocysts; if possible
permanent aeration is advisable
• Examine the faeces according to
section b)
b) Examination of faeces
using a modified McMaster-Method
• Oocysts of coccidia float on the
surface of a salt solution and are
concentrated there
• Flotation solutions:
- solution of ZnSO4, specific
gravity 1,30 g/ml
- solution of sugar (sucrose),
specific gravity 1,28 g/ml
- saturated solution of NaCl,
specific gravity 1,18 - 1,20 g/m
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• Principle: Flotation of nematode
eggs/oocysts of coccidia in a
counting chamber. The oocysts
float to just below the upper glass
while the debris sinks to the floor of
the counting chamber. The oocysts
are therefore clearly in focus and
may be counted under a defined
grid
• The unit is the number of oocysts
per gram of faeces = OPG
• Weigh out 4 g (or the complete
amount of the faeces in the petri
dish) of faeces into small plastic
bowls and suspend them in 15 ml
saturated NaCl solution; if the
faecal sample consists of pellets
use a mortar and pestle instead
• pass the solution through a tea
strainer and a funnel into a 100 ml
graduated cylinder
• fill up the cylinder with saturated
NaCl solution to 60 ml
• if it is not possible to collect 4 g of
faeces the amount of saturated salt
solution should be adapted (e.g. 2 g
faeces – 30 ml NaCl solution)
• add a magnetic rod and mix the
suspension with a magnetic stirrer
for about 2 min at highest turning
speed
• remove two portions of about 1
ml from the central vortex with a
pipette, discarding the first drop
each time
McMaster Slides
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c) Method for concentration
and washing of oocysts
• Suspend the faeces containing
the oocysts in water, It may be
necessary to use a mortar and
pestle
1
• transfer the rest of each portion
into one of the chambers of a
McMaster slide, avoid air bubbles
• 2 min flotation
• examine under the microscope at
magnification of x63, x100 or
x160 (depending on the size of
the parasite stages)
• Evaluation:
• Sensitivity of this method: 50 OPG
Mean number of oocysts
counted in both areas of the
chamber multiplied by 100 is
the oocyst count per gram of
faeces [OPG] = mean × 100
• Pass the suspension through a
strainer into 200 ml centrifuge
glasses and centrifuge them at
3000 rounds per minute
(rpm, = 2010 x g, Figs. 1-3)
2
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3
5
4
• Discard the supernatant (Figs. 3
and 4)
• Fill the centrifuge glasses with saturated NaCl solution (or another
flotation medium) and stir up the
sediment until there are no more
clots of sediment (Fig. 5)
• Another centrifugation (flotation of
oocysts)
• Collect the liquid from the surface
using a pipette (with the floating
oocysts) in a graduated 1,5-2 l
beaker containing 100 ml of water
(Figs. 6 and 7)
6
• Monitor the amount of oocysts left
in a centrifuge glass by examining
a drop from the surface under
the microscope, if there are many
oocysts left, collect them again
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8
7
• Dilute the collected oocyst suspension with water 1:5 (for example
200 ml oocyst suspension are
filled up to 1000 ml)
• The diluted oocyst suspension is
now filled in 50 ml Falcon-tubes and
centrifuged as described (Fig. 8)
• Discard the supernatant, stir up
the sediment, fill up with either
oocyst suspension that is left or
with water, and centrifuge again
(Figs. 8 and 9)
• The two former steps are repeated
two times with water in order to
wash the oocysts
9
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• Stir up the sediment of the last
centrifugation with 2% potassium
dichromate solution and store the
solution in petri dishes at room
temperature and regular aeration
• The oocysts can be differentiated
after the appropriate sporulation
time (4-5 days should be sufficient)
• Examine at least 100 sporulated
oocysts to determine the
proportion of Eimeria species in
the faecal sample
d) Criteria to determine the
Eimeria species by their
oocysts
• Oocyst size (small, medium, big)
• Oocyst shape (round,
subspherical, ellipsoidal,
cylindrical, ovoidal, pyriform,
tapering at one pole)
• Oocyst wall
• Colour (colourless, pale yellow,
yellowish-brown, brown)
• Surface (smooth, granular, with
protuberances, with striation)
• Micropyle
(yes/no/inconspicuous)
• Polar cap (yes/no)
• Oocyst and sporocyst residuum
(yes/no)
• Sporocyst shape (broad,
ellipsoidal, citron-like, elongate)
• Position of sporozoites in the
sporocyst (lying head to tail or
end to end)
Scheme of sporulated oocyst:
Polar body
Polar cap
Oocyst wall
Outer wall
Inner wall
hyaline
(=refractile
bodies
Micropyle
Stieda
body
Sporocyst
residuum
Sporocyst
Sporozoites
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B: Ovine Eimeria species
1. Oocysts without a
polar cap
a) Eimeria ovinoidalis
• Inconspicuous micropyle
• Sporocysts elongate to ovoidal
• Sporozoites lying head to tail in
sporocyst
• No Stieda body and no polar
body
b) Eimeria parva
• no micropyle
• sporocysts broad to ovoidal
• sporozoites lying head to tail in
sporocyst
• No Stieda body and no polar
body
Sporulated
Sporulated
Nonsporulated
Nonsporulated
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c) Eimeria pallida
• No micropyle
• Sporocysts elongate to ovoidal
• Sporozoites lying head to tail in
sporocyst
• No Stieda body
• Polar body may be absent
d) Eimeria faurei
• Distinct micropyle
• Sporocysts ovoidal
• Sporozoites lying head to tail in
sporocyst
• Stieda body and polar body
present
Nonsporulated
Sporulated
Nonsporulated
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2. Oocysts with a polar cap:
e) Eimeria marsica
• Polar cap indistinct or absent
• Micropyle inconspicuous
• Sporocysts elongate to ellipsoidal
• Sporozoites lying head to tail in
sporocysts
• Stieda body and polar body
present
f) Eimeria crandallis
• Micropyle present
• Polar cap may be absent
• Sporocysts broad to ellipsoidal,
citron-like
• Sporozoites lying end to end in
sporocysts (contrary to those of
E. weybridgensis)
• No Stieda body, but polar body
present
Sporulated
Sporulated
! Sporulated oocysts of
Eimeria crandallis need to be
differentiated from oocysts of
of E. weybridgensis!
Sporulated
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g) Eimeria weybridgensis
• Sporocysts elongate to ovoidal
• Sporozoites lying head to tail
(contrary to those of E. crandallis)
• No Stieda body present
• Polar body present
h) Eimeria bakuensis
• Micropyle present
• Sporocysts elongate to ellipsoidal
• Sporozoites lying head to tail in
sporocyst
• No Stieda body present
• Polar body present
Sporulated
Sporulated
! Sporulated oocysts of
E. weybridgensis need to be
differentiated from oocysts of
of Eimeria crandallis!
Nonsporulated
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i) Eimeria ahsata
• Micropyle with distinct polar cap
• Sporocysts elongate
• Sporozoites lying head to tail in
sporocyst
• No Stieda body present
• Polar body present
j) Eimeria granulosa
• Micropyle at the broad end of
oocyst, with distinct polar cap
• Sporocysts elongate to ovoidal
• Sporozoites lying head to tail in
sporocyst
• Stieda body and polar
body present
Sporulated
Sporulated
Nonsporulated
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k) Eimeria punctata
• Micropyle with polar cap
• wall with conspicuous, uniform,
cone-shaped pits (0.5 µm in
diameter)
• Sporocysts elongate to ovoidal
• Sporozoites lying head to tail in
sporocyst
• Stieda body and polar body
present
l) Eimeria intricata
• Micropyle with distinct polar cap
• Thick and striated wall
• Sporocysts elongate to ellipsoidal
• Sporozoites lying head to tail in
sporocyst
• Stieda body present
• Polar body absent
Sporulated
Sporulated
Nonsporulated
Nonsporulated
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Management and control
Coccidiosis in sheep flocks is usually associated with overstocking/
crowded conditions and faecal
contamination of drinking water or
feed. Improved hygienic
measurements and sanitation
generally reduces the infection rate
and the incidence of clinical disease
outbreaks. Frequent cleaning of
pens and the use of feeders and
water containers designed to
prevent fecal contamination of feed
and water. Feeding silage, hay or
corn stalks to the group significantly
increases the risk of coccidiosis
(Foreyt, 1986). Proper stocking
rates reduce the numbers of oocysts
as well as reducing stress, which
may lower resistance of sheep and
exacerbate coccidian infections.
Providing a proper diet and
adequate shelter will also reduce
stress-related coccidiosis.
Affected sheep should be isolated, and special care taken on
them so that their faeces do not
contaminate the feed and water of
unaffected sheep.To prevent pasture coccidiosis, animals should
not be turned out onto heavily
contaminated pastures, especially
in the first grazing season. Young
animals should be kept off heavily
contaminated pastures when they
are most susceptible (Taylor and
Catchpole, 1994).
The eradication of coccidiosis
does not seem feasible because
of its widespread prevalence, the
enormous reproductive potential
of the parasite, and the oocysts’
ability to survive in the environment
for a long time. Accepting this
fact is important to establishing a
successful program to control the
disease.
The overall philosophy of
coccidiosis control is to prevent
clinical signs of the disease through
the use of proper sanitation and the
administration of an anticoccidial
before anticipated outbreaks. Proper
administration of anticoccidial
remedies products can significantly
reduce or eliminate clinical
coccidiosis in sheep (Foreyt, 1986).
Normally all lambs in a flock should
be treated as even those showing
no symptoms are likely to be
infected (Taylor, 1995).
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It is important to keep in mind that
once lambs have started scouring,
anticoccidial therapy will have a
limited effect on preventing the
consequences of the disease. The
setback suffered is virtually
impossible to compensate for later.
The establishment of programs that
combine management strategies,
farm hygiene measures and
strategic chemotherapeutic
intervention is very important for
reducing the infection pressure of
the parasite and limiting the effects
of the disease on the animals.
Although Eimeria sp. are resistant
to the majority of common
disinfectants, there are some reports
of a reduction in the number of
oocysts when compounds that are
able to penetrate the oocyst wall are
used (combination of phenolic and
alcoholic compounds or ammonia in
a 50% solution).
A typical bedding for indoor sheep flocks
Grazing lamb
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A single oral application of
Baycox® 5% at a dose rate of
20 mg/kg prevents clinical
coccidiosis, weight gain reduction
and reduces oocysts shedding.
Toltrazuril does not interfere with
the natural immunity and allows
animals to build up natural immunity
because it does not kill the extra
cellular living stages (sporozoites
and merazoites) thereby allowing
them to attach to mucosal cells
for the induction of immunitiy.
For example, decoquinate and
monensin are active ingredients
which kill the extracellular stage of
coccidia such as sporozoites and
merazoites.
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Baycox® 5% (Toltrazuril) for Lambs
Active Ingredient
International Nonproprietary Name (INN)
Toltrazuril (generic name)
Composition
Each ml of Baycox® 5%
contains 50 mg of toltrazuril.
Chemical name:
1-[3-methyl-4(41-trifluoromethylthiophenoxy) phenyl]-3-methyl-1,3,5triazine-2,4,6- (1H,3H,5H)-trione
or
1-Metyl-3-[4-[p[(trifluoromethyl)thio]phenoxy]-mtolyl]- s-triazine-2,4,6(1H,3H,5H)trione
Molecular formula:
C18H14F3N3O4S
Structural formula:
Molecular weight: 425.38
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Spectrum of Activity
Toltrazuril is active against various
coccidia species in mammals (cattle
and pig) and birds (poultry),
including Eimeria crandallis and
Eimeria ovinoidalis in sheep.
Mode of Action
Clinical and electron microscopical
studies show that toltrazuril is active
against all intracellular development
stages of coccidia, including
schizonts, microgamonts and
macrogamonts. It interferes with
division of the protozoal nucleus,
the activity of the mitochondria, and
damages the wall-forming bodies in
the microgametes. Toltrazuril
produces severe vacualisation of the
protozoal endoplasmic reticulum in
all intracellular development stages
and the type of action is
anticoccidial (data on file).
Pharmacokinetics
After oral administration toltrazuril is
slowly absorbed in mammals. The
main metabolite is characterised as
toltrazuril sulfone. The maximal plasma
concentration (Cmax = 62 mg/L) was
observed 2 days following oral
administration. The elimination of
toltrazuril is slow with an elimination
half-life time of approximately 9 days.
The major route of excretion is via the
faeces.
Amounts to be administered
and administration route
Each animal should be treated with a
single oral dose of 20 mg toltrazuril/
kg body weight corresponding to 0.4
ml oral suspension per kg body
weight. To obtain maximum benefit,
animals should be treated before the
expected onset of clinical signs, i.e. in
the prepatent period.
If animals are to be treated collectively
rather than individually, they should be
grouped according to their body
weight and dosed accordingly, in
order to avoid under- or overdosing.
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Adverse reactions
None known
Interactions with other medicinal products and other
forms of interaction
None known
Other special information
Laboratory studies in rat and rabbit
have not produced any evidence of
a teratogenic, foetotoxic or maternotoxic effect.
Other special information
No signs of overdose have been
observed in target animal safety studies
with threefold overdose at a single
treatment and twofold overdose at
treatment on two consecutive days.
Withdrawal periods
Please follow the instruction of your
local authority for withdrawal period.
Presentation
Baycox® 5% is available in different
packages to suit local market conditions. Please contact your local Bayer
office for details on pack size and type.
Storage conditions
Keep out of reach of children and
uninformed persons.
Treatment Time
The timing of a preventive treatment
depends normally on the farm
history and on the rearing system
such as indoor (inhouse or intensive
rearing) and outdoor (grazing and
extensive rearing) system. And
relocation of lambs to contaminated paddocks within a herd is also
a depending factor for the timing of
a preventive treatment. The prepatent period (the time from uptake
of infection/oocysts to the start of
oocyst excretion) is variable among
different Eimeria sp. in sheep. This
period must be taken into account
when the treatment initiated. The
most important and pathogenic
Eimeria sp. such as Eimeria crandallis and Eimeria ovinoidalis have
a prepatent period of 15-20 days
and 12-15 days respectively.
Therefore preventive treatment of
lambs should be initiated before the
expected onset of disease and
before the first oocysts are seen in
the feces. It is evident from the life
cycle of the parasite that the
asexual and sexual phases inflict
severe damage to the intestine, and
oocysts are excreted after the
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damage has already been done.
The intestinal damage during the
prepatent period can be severe.
The timing of therapeutic control is
important for achieving optimal
results. Treatment during the
prepatent period ensures that
animals will not suffer clinical
disease. Treatment after oocysts are
seen in the faeces would only
prevent further deterioration of
disease.
Coccidiosis is dynamic and
insidious on a farm where different
animals are at different stages of
disease development (depending
on the infective dose and time of
infection). However, one can
deduce the suitable time of
treatment (approximately one week
before anticipated clinical signs)
depending on the history of the
farm and prior coccidiosis
episodes.
The mechanism of action (activity
against all intracellular
development stages of coccidia)
and kinetic behaviour of Baycox®
(persistency in the body) give a
long lasting window ensuring that
most of the developing stages of
the parasites are killed and animals
do not suffer clinical signs.
Furthermore, Baycox® not only
controls coccidia infection without
impairing the ability of animals to
acquire immunity, thus promoting
resistance to reinfection (Steinfelder
et al., 2005).
The following points should
be taken into account when
controlling and managing
coccidiosis in a sheep flock:
Diarrhoea or poor
performers in your flock?
Suspect coccidiosis
• Flock history of watery or
haemorrhagic diarrhoea
unresponsive to antibiotic
treatment.
• Diarrhoea associated with
pasturing (around 2 weeks after
pasturing).
• Diarrhoea associated with
management practices: indoor
intensive management requires
special care.
• Poor weight gain and retarded
growth.
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Diagnosis of the disease
• Faecal examination for OPG
and identification of pathogenic
Eimeria species (E. crandallis, E.
ovinoidalis) in the laboratory with
the appropriate test.
• Pre-patent period varies between
Eimeria species:
E. crandallis
15 - 20 days
E. ovinoidalis
12 - 15 days
Take faeces samples directly from
the rectum in suspected lambs in
2 or 3 weeks after relocation in
contaminated paddocks or pasturing. Examine the faeces according
to the procedure in the chapter
diagnosis.
• Administer a single oral treatment
of Baycox® 5% based on 20 mg/kg
toltrazuril to the lambs.
• When the animals are treated
after exhibiting clinical signs and
recover the damage already
inflicted to the intestine still affects
the production parameters. This
can be prevented with a
metaphylactic treatment of the
animals during the prepatent
period.
• It is advisable to establish
metaphylactic programmes in the
flocks to avoid the detrimental
effects on intestinal mucosa and
high costs related to coccidiosis.
Set up a treatment schedule
for the flock
• Adjust the time of treatment of the
flock according to the management
practices (indoor management,
outdoor management, pasturing,
etc.), the coccidia species present in
the flock and the history of onset of
diarrhoea.
• To prevent the losses associated
with coccidiosis treatment should
be given before clinical signs
appear.
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Efficacy Trials
Clinical trials:
Naturally infected lambs have been
treated with toltrazuril 20 mg/kg
BW 10 days after turn out onto
pasture. The oocyst excretion was
observed up until 9 weeks of age vs
an untreated control group (Taylor
and Kenny, 1988). Treatment with
Baycox significantly controlled the
oocyst excretion during the course of
the study (5 weeks). The results have
been presented in the figure 13.
% lambs with positive
OPG in each group
(100 % equivalent to
137,897 opg)
Figure 13. Efficacy of Baycox for the control of natural coccidiosis in lambs
(Taylor and Kenny, 1988; modif.)
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The metaphylactic efficacy of
toltrazuril was studied by Gjerde
and Helle (1991) in Norway. Seven
to 9 days after turnout on pasture
lambs were treated with toltrazuril at
20 mg/kg to prevent coccidiosis.
Treatment with Baycox reduced the
oocysts output significantly and
prevented the development of
diarrhoea and improved weight
gain during the first 4 – 5 weeks
after treatment. Results have been
presented in figures 14 – 17.
Figure 14. Effect of one toltrazuril treatment (20 mg/kg) on day 7 or 10 after turn out on the fecal
oocyst out put of lambs naturally infected with coccidian (Gjerde and Helle, 1991).
*: anthelmintic treatment on the weekly basis (5 mg/kg febantel), OPG: oocysts per gram feces
Stafford et al. (1994) studied the
efficacy of weekly treatment with
Baycox in a group of 2-6 weeks
old suckling twin lambs in New
Zealand. One of each set of twins
was treated with Baycox (20 mg
toltrazuril /kgBW) per os. Faecel
samples were collected per rectum
from each lamb once weekly for
the first 6 weeks and thereafter at
14-day intervals. All lambs were
treated with a levamisole-based
anthelmintic at week 2 and week
6. The mean oocysts count and
liveweight were calculated on
a weekly basis for the treatment
and control groups. Treatment
with Baycox provided significantly
reduced OPG and generally better
weight gain development during
the course of the study. The mean
liveweight of the control and treated
groups at the beginning of the trial
was 7,9 and 8,0 kg respectively
and at the end of the trial 19,8
and 21,0 kg. The difference in the
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Figure 15. Daily weight gain development in lambs treated with toltrazuril or toltrazuril +
anthelmintic on day 7 after turnout to pasture (Gjerde and Helle, 1991).
Figure 16. Effect of a single toltrazuril (Baycox) treatment (on day 7 or 10 after turnout) on faecal
consistency (diarrhoea score) of lambs naturally infected with coccidian (Gjerde and Helle 1991).
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overall weight gain between the
control and treated group 11,9 and
13,0 kg respectively, was significant
(p<0,05). Results were presented in
figure 18 – 19.
In a commercial sheep farm in
France, lambs (n:25 in each group)
were treated with Baycox 5%
(20 mg/kg bw toltrazuril) and
diclazuril (1 mg/kg bw). An other
group of lambs served untreated
control group. The lambs were kept
with their mother in one of sheepfold under same condition and they
were 10-14 days old when were
treated with one of the drug above.
The prevalence of oocysts excretion,
OPG and daily weight gain were
determined during the course of the
study (Fig 20, 21 and 22 and table
5). Metaphylactic treatment with
Baycox 5% significantly reduced
enviromental contamination with
oocysts and improved weight gain
in comparison to an untreated
control and a matched
diclazuril-treated group of animals,
demonstrating the beneficial effects
of this treatment in subclinical or
mild coccidiosis in young lambs.
Study has been accepted for the
publication in Parasitology Research
(Le sueur et al. 2008).
Figure 17. Effect of a single toltrazuril treatment 7 days after turnout on faecal consistency
(diarrhea score) of lambs naturally infected with coccidian (Gjerde and Helle 1991).
44
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Figure 18. The mean OPG of 43 sets of twin lambs, one of which was treated with Baycox
(20 mg/kg) once weekly (Baycox group) and one of which was in an untreated control group
(Stafford et al. 1994).
Figure 19. The mean live weight of 43 sets of twin lambs, one of which was treated with Baycox
(20 mg/kg) once weekly and one of which was in an untreated control group (Stafford et al. 1994).
45
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Fig 20. Excretion prevalences during the study in the untreated control group,
the diclazuril-treated group and Baycox 5% (toltrazuril) treated group (Le sueur et al. 2008).
Fig 21. Average oocysts excretion in the groups treated with diclazuril, Baycox 5% and control
group during the course of sampling given as LN (OPG+1) (Le sueur et al. 2008).
46
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Fig 22. Daily weight gain of lambs in control, Baycox 5% and Diclazuril groups during
study days 0 - 60 (Le sueur et al. 2008).
Table 5. Qualitative and quantitative oocyst excretion in the groups treated
with diclazuril, Baycox 5% and control group (Le sueur et al. 2008).
Group
n
Excretion at
least once (%)
Average excretion days in
% (minimum-maximum)
Mean OPG x 103
(maximum OPG x 103)
Control
25
100
49.5
(25-83.3)
526
(16074)
Diclazuril
25
92
25.3
(0.0- 50)
21
(1278)
Baycox 5%
25
68
12.8
(0.0 – 33.3)
5.2
(1226)
47
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