veterinary

parasitology

ELSEVIER VeterinaryParasitology 65 (1996) 89-97

Efficacy of an in-feed formulation of ivermectin

against adult worms and somatic larvae of
Strongyloides ransomi
D. Barth ~'* S. Rehbein" J.F.S. Reid b R.A. Barrick c
a Merck Research Laboratories, 83101 Rohrdorf-Lauterbach, Germany
b Merck Research Laboratories, Clos du Lynx 5, Bruxelles, Belgium
e Merck Research Laboratories, Rahway, NJ 07065, USA

Received 14 August 1995; accepted 28 November 1995

Abstract

The efficacy of an in-feed formulation (IVOMEC ® premix) containing 0.6% ivermectin was
tested against Strongyloides ransomi in swine.
The efficacy of ivermectin against patent infections of S. ransomi when given via the feed at 2
ppm for 7 days (Days 0-7) to provide 100 mcg ivermectin kg -~ body weight day-~ was
evaluated in a study with 16 3-month-old male castrated piglets. Seven days prior to treatment
each piglet was infected subcutaneously with 2500 infective larvae of S. ransomi. Fecal egg
counts were carded out on Days - 7 , 0, 7 and 14, and worm counts on Day 14. Efficacy was
100% in all treated piglets.
Two trials involving 40 pregnant gilts were carded out to evaluate the efficacy of ivermectin
against the somatic larval stages of S. ransomi when given at a daily dose of 100 mcg kg- 1 body
weight for 7 days starting on Days 66, 78, 92 or 103 of pregnancy. The gilts were each
experimentally infected with three subcutaneous injections of 250000 infective larvae, with the
last infection given between 12 and 30 days prior to commencement of treatment. Gilts were
confirmed free of pre-existing intestinal stages of S. ransomi prior to ivermectin treatment. Fecal
nematode egg counts were carded out in gilts/sows and piglets subsequently born. The Strongy-
loides larvae present in sow milk 1, 2 and 7 days post partum were counted. Fourteen days post
nature, worm counts were performed in four randomly selected piglets from each litter. IVOMEC ®
premix given to pregnant gilts prevented shedding of larvae in sow milk, egg output in feces and
the establishment of S. ransomi in piglets.

Keywords: Pig; Nematoda; Strongyloides ransomi; Ivermectin;Control methods

* Corresponding author. Tel.: 49-8032-501l; fax: 49-8032-1310.

0304-4017/96/$15.00 Copyright © 1996 Elsevier Science B.V. All rights reserved.

PII S0304-401 7(96)00939-9
90 D. Barth et al./ Veterinary Parasitology 65 (1996) 89-97

1. Introduction

Strongyloides ransomi is an extraordinary nematode. Not only is it a common

endemic parasite of swine (Aka, 1994), but it may also complete a free-living life cycle.
The parasitic generation consists only of parthenogenetic females located in the small
intestine. Adult worms are primarily found in suckling piglets whereas sows commonly
host somatic larval stages. Infections may be acquired by ingestion, skin penetration and
most importantly by transcolostral passage of infective third-stage larvae from the sow
to the newly born piglets (Moncol and Batte, 1966).
The enteric stages of S. ransomi have been shown to be susceptible to thiabendazole
(Leland et al., 1968; Pfeiffer and Supperer, 1969), cambendazole (Egerton et al., 1970;
Enigk and Dey-Hazra, 1971) and parenterally administered ivermectin (Barth et al.,
1980; Stewart et al., 1981; Brokken et al., 1983; Gill et al., 1990).
The somatic third-stage larvae found in the sow are much more refractory to
treatment (Moncol and Batte, 1971; Enigk et al., 1974; Barth, 1980). Murrell (1981)
demonstrated an efficacy of 87% against arrested L 3 in the subventral fat of fattening
pigs when ivermectin was given intramuscularly at 600 mcg kg -~. When given at the
recommended single dose of 300 mcg kg- ~ subcutaneously to sows once, 4 to 16 days
before farrowing, ivermectin was highly effective against somatic S. ransomi larvae as
judged by counts of larvae in milk and the worm burdens of piglets (Barth and Preston,
1985).
This paper reports the results of three controlled studies designed to evaluate the
efficacy of ivermectin in an in-feed formulation against adult S. ransomi in piglets (Trial
1) and its ability to prevent transmission of somatic larvae from the sow to its progeny
(Trials 2 and 3).

2. Materials and methods

2.1. Animals

2.1.1. Trial 1
Sixteen male-castrate crossbred piglets (Deutsches Edelschwein × Pietrain) weighing
between 25.6 and 33.6 kg and approximately 3 months old, were used for the study
against adult S. ransomi. The animals were born and raised under worm-free conditions.

2.1.2. Trials 2 and 3

Forty pregnant Deutsches Edelschwein (10-12 months old) gilts weighing between
123.2 and 186.0 kg at time of treatment, and from a S. ransomi free herd, were used for
the studies against somatic larvae. In both studies the gilts used were inseminated on two
different dates. Within each date the gilts were ranked according to body weight before
the start of the first treatment period to form replicates of three gilts each. In each trial
the gilts of Replicates 1-3 and 4-6 (Trial 3) or 4-7 (Trial 2) were artificially
inseminated on the same day.
 D. Barth et al./ Veterinary Parasitology 65 (1996) 89-97 91

2.2. Infection

A recently isolated field strain of S. ransomi originating from Northern Germany and
maintained by two (Trial 3) or three (Trials 1 and 2) passages was used. The larvae were
cultured from feces of infected donor animals and stored at room temperature until use.
At time of infection they were 1 - 3 days old.
The piglets were each infected with 2500 larvae of S. ransomi by subcutaneous
injection in the inguinal region 7 days prior to treatment. The gilts, were infected with
250000 infective larvae by subcutaneous injection in the neck, on each of three
occasions between the 34th and 80th day of gestation (Table 1). After artificial infection
all gilts were treated with thiabendazole. At 50 mg kg-1 this compound removes any
enteric stages of S. ransomi, which might act as a source of infection to the piglets,
however, it has no significant effect against somatic larvae of S. ransomi. This was done
in Trial 2 10 days after last infection while in Trial 3 all gilts were treated 7 days after
last infection. As some Strongyloides eggs were found in the feces of control gilts of
Trial 3 21 days after last infection the control gilts were treated a second time the
following day to avoid infection of piglets via larvae derived from their feces.

2.3. Treatment

In Trial 1 eight replicates of two piglets of similar body weight were formed to
evaluate efficacy against adult S. ransomi. Within a replicate one animal was allocated
randomly to an untreated control group or to treatment with ivermectin (0.6% I V O M E C ®
premix, MSD AgVet) included in the complete ration at 2 ppm to provide 100 mcg
ivermectin kg-n body weight day -1. Medicated feed was given ad libitum from Day 0
to Day 7.
In Trials 2 and 3 replicates of three animals with similar body weight and same
insemination day were formed to evaluate efficacy against somatic larvae of S. ransomi.
Within replicates, the animals were randomly allocated to an untreated control group or
to a treatment group with ivermectin (0.6% IVOMEC ® premix, MSD AgVet) at 100

Table 1
Design of Trials 2 and 3 with gilts to evaluate efficacy of ivermectin against somatic larvae of S. ransomi
Trial 2 day Trial day Trial 3 day Trial day Event
of pregnancy of pregnancy
34 - 66 - Artificial infection
41 - 73 - Artificial infection
48 - 80 - Artificial infection
58 - 87 - Deworming with thiabendazole
66-72 0-6 92-98 0-6 Treatment of Group 2
102 10 Second deworming of control
group with thiabendzole
78-84 12-18 103-109 11-17 Treatment of Group 3
92 D. Barth et al. / Veterinary Parasitology 65 (1996) 89-97

mcg kg- l body weight day- ~ in mid pregnancy on Days 66 to 72 or 78 to 84 (Trial 2)

and in late pregnancy on Days 92 to 98 or 103 to 109 (Trial 3) of pregnancy (Table 1).
Treatments were administered via medicated feed containing 10 ppm ivermectin. Each
gilt was fed with a specific amount of medicated feed based on her body weight
recorded immediately before start of treatment period. Half of the dose was fed in the
morning, the other half in the evening. After consumption of the medicated feed
unmedicated feed was given up to 1.1 kg (Trial 2) or 1.25 kg (Trial 3).

2.4. Management

To preclude cross infections with S. ransomi between animals, piglets (Trial 1) were
housed individually starting 14 days prior to treatment. The gilts in Trials 2 and 3 were
transferred to individual pens 8 and 5 days, respectively, before start of ivermectin
treatment.
The piglets in Trial 1 received a commercial ration for growers ad libitum.
The feed for the gilts was a mixture of 50% commercial concentrate plus 50% wheat
bran. During the medication period animals were restricted fed twice daily, while the
feed was offered ad libitum at other times. Suckling piglets from Trials 2 and 3 were
offered unmedicated concentrate feed ad libitum from Day 7 post natum onwards.

2.5. Parasitological investigations

Fecal nematode egg counts (EPG) were carried out using a flotation method with
saturated sodium chloride solution and a detection limit of 10 eggs g-I feces. Feces of
piglets was investigated in Trial 1 7 days prior to treatment, at start and end of the
treatment period and 1 week later. In Trials 2 and 3 this was done when piglets were 7
and 14 days old. The feces of gilts was investigated 7 and 28 days post infection and 7
and 14 days post parturition. In Trials 2 and 3 the number of Strongyloides larvae
present in 100-ml samples of gilt's milk was also counted. A specially designed milking
machine was used to milk the gilts (Visser and Zech, 1985). Milk flow was stimulated
by intravenous injection of 10 to 15 IU of oxytocin. The milk samples were centrifuged
at 1500 rpm for 5 min. The supernatant was removed and filled up with tap water. This
process was repeated until the supernatant was clear and all larvae present in the
sediment could be counted microscopically.
In Trial 1 all piglets were necropsied 7 days after termination of treatment while in
Trials 2 and 3 four piglets from each litter were selected randomly from each litter for
necropsy 14 days post natum using a die after ranking the piglets according to body
weight within sex.
The small intestine of the necropsied animals was removed, opened and the contents
washed through a 0.15-mm sieve. The residue was collected and the worms present in
two aliquots of 20% each were counted.
Geometric means were calculated for worm counts, larval counts and egg counts. The
means were compared using Wilcoxon's rank sum statistic and a two-sided significance
level of P = 0.05.
 D. Barth et al. / Veterinary Parasitology 65 (1996) 89-97 93

3. Results

The results o f Trial 1 showed that ivermectin given in a complete ration at 2 ppm for
7 days was 100% effective ( P < 0.01) against an established infection of adult S.
r a n s o m i (Table 2).
Feed consumption or weight gain was not influenced by medication o f the feed.
During the medication period the treated pigs consumed 54.5 g k g - 1 body weight daily
while the controls ate 52.9 g, calculated on body weight at D a y 7. The mean daily
weight gain per pig during the treatment period was 713 g in the control group and 750
g in the treated group.
In Trial 2 S. ransomi eggs were recovered from feces o f all gilts 7 days post last
infection, while after treatment with thiabendazole no animal excreted eggs. Larvae o f S.
r a n s o m i were present in the milk of all control animals with the highest mean numbers
observed on the first day and lowest numbers 7 days post partum. N o larvae were
recovered from the milk o f animals treated with ivermectin for 7 days commencing 48
to 49 days (Group 2) or 34 to 39 days (Group 3) before parturition. At necropsy 14 days
after parturition all control piglets were infested with a mean burden o f 632 S. ransomi
and a range of 195-2003 worms. N o worms were recovered from the litters o f gilts
treated with ivermectin (Table 3). After assignment, two animals were removed from the
control group, one which aborted on Day 4 (Day 70 of pregnancy) and another which

Table 2
Trial 1. Efficacy of ivermectin vs adult S. ransomi in piglets when given orally at a rate of 2 ppm in complete
ration for 7 days
Control lvermectin,
untreated 2 ppm
Number of piglets 8 8
EPG a
Day - 7 0 0
Day 0 30.4 36.1
Day 7 280.9 0b
Day 14 87.8 0b
Efficacy (%) - 100
Worm count
Mean a 1105.3 0
Range 650-1400 0
Efficacy (%) - 100
Body weight c (kg)
Day - I 29.2 28.9 b
Day 7 34.9 34.9 b
Feed consumption e (g)
Days 0-7 12931 13229 b

a Geometric mean based on transformation In(count + 1).

b Based on seven pigs (one pig died on Day 3 due to verrucose endocarditis).
c Arithmetic mean.
94 D. Barth et aL / Veterinary Parasitology 65 (1996) 89-97

Table 3
Trial 2. Efficacy of ivermectin against somatic larvae of S. ransomi in gilts when given orally at a daily dose
of 100 mcg kg- ~ body weight for 7 days during mid pregnancy
Control lvermeetin during gestation days
untreated 66-72 78-84
Number of gilts with litter 5 7 7
Duration of pregnancy (days) 113-116 114-115 112-117
Number a of piglets per litter
Bona 10.2 10.7 8.4
At 14 days 7.60 8.00 6.00
Weight a (g) of piglets
At birth 1147 1211 1213
At 14 days 3573 3590 3249 b
E I ~ e of gilts
7 days post infection l 145 1334 957
28 days post infection 0 0 0
7 days post parturition 0 0 0
14 days post parturition 0 0 0
E I ~ ¢ of piglets
At 7 days 81 l 0
At 14 days 5057 0 b
Larvae counts c lOOml- l milk
1 day post partum 23.0 0
2 days post partum 16.1 0
7 days post partum 0.9 0b
Count c of S. ransomi per piglet
At 14 days 632 d 0 0 d
Efficacy (%) 100 100

a Arithmetic mean.
b Counts from four piglets of four sows each and two piglets of one sow.
c Geometric mean based on transformation In(count+ 1).
a Based on six sows (one sow had no milk and piglets died within 1 day).

did not b e c o m e pregnant. In G r o u p 3 one animal was v e r y a g g r e s s i v e and killed its

piglets within 1 day post partum.
In Trial 3 S. r a n s o m i e g g s w e r e present in feces o f all gilts 7 days p o s t infection but
not after treatment with thiabendazole. W h i l e Strongyloides larvae w e r e present in milk
o f all control gilts n o larvae w e r e seen in the m i l k o f gilts treated with i v e r m e c t i n for 7
days starting 2 0 - 2 4 days ( G r o u p 2) or 8 - 1 3 ( G r o u p 3) days b e f o r e farrowing. The m e a n
w o r m burden o f control piglets necropsied at an age o f 14 days w a s 553 S. ransomi with
a range o f 1 1 3 - 1 6 3 3 w o r m s . E f f i c a c y was > 9 9 % ( P < 0.01) for those litters f r o m gilts
treated f r o m D a y 92 to 98 o f gestation and 100% for those treated f r o m D a y 103 to 109
(Table 4). In Trial 3 one control gilt did not a l i o w its piglets to suckle and all piglets
died within 4 days.
 D. Barth et al. / Veterinary Parasitology 65 (1996) 89-97 95

Table 4
Trial 3. Efficacy of ivermectin against somatic larvae of S. ransomi in gilts when given orally at a daily dose
of 100 mcg k g - i body weight for 7 days during late pregnancy
Control lvermectin during gestation days
untreated 92-98 103-109
Number of gilts with litter 6 6 7
Duration of pregnancy (days) 112-116 112-116 111-116
Number a of piglets per litter
Born 8.33 8.17 11.14
At 14 days 6.33 b 7.67 9.57
Weight a (g) of piglets
At birth 1423 1354 1260
At 14 days 3501 b 3827 3318
EPG ¢ of gilts
7 days post Infection 3842 3191 2238
28 days post infection 0 0 0
7 days post parturition 0 0 0
14 days post parturition 2 0 0
EPG c of piglets
At 7 days 153 b 0.1 d
At 14 days 1720 b 0.1 a
Larvae counts b 100ml- ~ milk
1 day post partum 8.8 0
2 days post partum 5.7 0
7 days post partum 2.2 b 0
Count c of S. ransomi per piglet
At 14 days 553 b 0.2 d 0
Efficacy (%) - > 99 100

a Arithmetic mean.
b Based on five sows. One sow removed from trial 4 days post partum, after all her piglets died.
c Geometric mean based on transformation In(count + 1).
d A single piglet.

In none of the trials an adverse reaction attributable to IVOMEC ® premix was

observed.

4. Discussion

Our results show that ivermectin given orally at 2 ppm in a complete ration over a
period of 7 days was highly effective (100% efficacy) against adult S. ransomi. This
level of efficacy is equivalent to that provided by a single injection of 300 mcg
ivermectin kg -~ body weight (Benz et al., 1989; Gill et al., 1990; Xie et al., 1991).
Somatic larvae do not continue their development until they are transmitted by the
mother to her offspring. This was confirmed by the fecal examinations of the gilts which
showed that after successful treatment of the enteric infection with thiabendazole gilts
did not shed Strongyloides eggs throughout until the trial was terminated 14 days post
96 D. Barth et a l . / Veterinary Parasitology 65 (1996) 89-97

parturition. As fecal excretion in the sows was controlled the only source of infection in
piglets could have been the somatic larvae in the colostrum.
While a number of anthelmintics are available for treatment of patent infections of S.
ransorai, ivermectin is the only compound which has also been shown to be effective
against the somatic larvae of this parasite. The results show that transfer of S. ransomi
larvae to suckling pigs via milk or colostrum was prevented when sows were treated
with oral ivermectin at 100 mcg kg-~ day-~ for 7 consecutive days during pregnancy.
The studies reported here also confirmed that the high efficacy of oral ivermectin against
somatic larvae in the pregnant sow is similar to that seen after a single injection at a
dose rate of 300 mcg ivermectin kg- ] body weight (Barth and Preston, 1985).
Treatment was equally efficacious whether given in mid or late pregnancy. Conse-
quently the timing of treatment of S. ransomi, using a convenient in-feed formulation of
ivermectin can be flexible. It allows herd treatment to commence on any day during mid
to late pregnancy and other factors can be taken into account such as the best timing of
treatments for other parasites which the farmer might want to control.

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