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Effect of treatment with phytosterols in three herds with porcine respiratory

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Case ­study Peer ­reviewed

Effect of treatment with phytosterols in three herds with

porcine respiratory disease ­complex
Lorenzo J. Fraile, DVM, PhD; Elisa Crisci, DVM; Joan Weenberg, DVM; Montse Armadans, DVM; Lorenzo Mendoza, DVM; Lara
Ruiz, DVM; Santi Bernaus, DVM; María Montoya, MSc, ­PhD

Summary administered in feed during the nursery evaluated, except feed conversion ratio,
This case study includes three pig produc- and finishing periods, from 4 weeks before when assessed using SPC criteria in Sys-
tion systems belonging to two companies in until 4 weeks after the predicted date of tems One and Two and one-way ANOVA
Spain. Mortality, percent culls, average daily an outbreak of porcine respiratory disease in System Three. Phytosterols may be use-
gain (ADG), and feed efficiency in Produc- complex (PRDC). In Production System ful to control endemic PRDC under field
tion Systems One and Two were incorpo- Three, data obtained for batches treated or ­conditions.
rated into a database program and analyzed not treated with Inmunicin Maymo were
Keywords: swine, phytosterols, porcine
using statistical process control (SPC) compared using a one-way ANOVA, with
respiratory disease complex, inmunomodu-
techniques to assess changes in performance the level of significance set at .05. In all
lation, statistical process ­control
before and after phytosterols, natural three production systems, finisher mortality
substances that act as immunomodulators, and percent culls were lower and production Received: November 16, 2007
were added to the feed. Inmunicin Maymo parameters were best when the immuno- Accepted: February 6, 2008
(Maymo Laboratories SA, Barcelona, Spain), modulator was applied. Differences were
a commercial phytosterol product, was statistically significant for all parameters

Resumen - Efecto del tratamiento con fitoesteroles, se administró en el alimento los Sistemas Uno y Dos y la ANOVA de
fitoesteroles en tres hatos con complejo durante los periodos de destete y final- una vía en el Sistema Tres. Los fitoesteroles
respiratorio porcino ización, desde 4 semanas antes hasta 4 pueden ser útiles para controlar el PRDC
Este estudio de casos incluye tres sistemas semanas después de la fecha predicha de endémico bajo condiciones de campo.
de producción de cerdos que pertenecen un brote de complejo respiratorio porcino
a dos compañías en España. En un pro- (PRDC por sus siglas en inglés). En el
grama de base de datos se integraron la Sistema de Producción Tres, la información
Résumé - Effet d’un traitement aux phy-
mortalidad, el porcentaje de desechado, obtenida de grupos tratados y no tratados
tostérols dans trois troupeaux aux prises
ganancia diaria promedio (ADG por sus con el Inmunicin Maymo se comparó utili-
avec le complexe des maladies respira-
siglas en inglés), y eficiencia alimenticia zando un ANOVA de una vía, con un nivel
toires porcines
de los Sistemas de Producción Uno y Dos de significancia establecido a .05. En los
y se analizaron utilizando la técnica de tres sistemas de producción, la mortalidad La présente étude de cas inclus trois sys-
control estadístico del proceso (SPC por en las engordas y el porcentaje de desechos tèmes de production appartenant à deux
sus siglas en inglés) para evaluar cambios fueron más bajos y los parámetros de pro- compagnies en Espagne. Les donnés sur
en el desempeño antes y después de que ducción fueron mejores cuando se aplicó el les mortalités, le pourcentage de réforme,
los fitoesteroles, sustancias naturales que inmunomodulador. Las diferencias fueron le gain quotidien moyen (ADG), et
actúan como inmunomoduladores, se estadísticamente significativas en todos los l’efficacité alimentaire pour les Systèmes de
añadieran al alimento. Inmunicin Maymo parámetros evaluados, excepto en el índice Production Un et Deux ont été incorporées
(Laboratorios Maymo SA, Barcelona, de conversión alimenticia, cuando se evalu- dans un programme de base de données et
España) un producto comercial a base de aron utilizando los criterios del SPC en analysées à l’aide de techniques utilisant un
processus de contrôle statistique (SPC) afin
d’évaluer les changements dans les perfor-
LJF, EC, MM: Centre de Reçerca en Sanitat Animal (CReSA), Edifici V, Universitat Autónoma de mances avant et après que des phytostérols,
Barcelona, Bellaterra, ­Spain. substances naturelles qui agissent comme
LJF, MM: Institut de Recerca i Tecnologies Agroalimentaries (IRTA), Barcelona, ­Spain. des immunomodulateurs, aient été ajoutés
aux aliments. Immunicin Maymo (Maymo
JW, MA, LM, LR: Pinsos Baucells, Seu central Tona, Barcelona, ­Spain.
Laboratories SA, Barcelone, Espagne),
SB: Avinguda Alcalde Rovira Roure, 110, Lleida, ­Spain. un produit phytostérol commercial, a été
Corresponding author: Dr Lorenzo J. Fraile, CReSA, Edifici V, Universitat Autónoma de administré dans l’alimentation durant les
Barcelona, 08193 Bellaterra, Spain; Tel: +34 93 581 44 95; Fax: +34 93 581 44 90; E-mail: périodes en pouponnière et en finition,
­[Link]@[Link]. d’une période allant de 4 semaines avant
à 4 semaines après la date prévue d’une
This article is available online at [Link]
éclosion du complexe des maladies respira-
Fraile LJ, Crisci E, Weenberg J, et al. Effect of treatment with phytosterols in three herds with toires porcines (PRDC). Dans le Système
porcine respiratory disease ­complex. J Swine Health Prod. 2009;17(1):32-41. de Production Trois, les données obtenues
32 Journal of Swine Health and Production — January and February 2009
pour les lots traités ou non-traités avec modulate the immune system, helping companies located in northeastern Spain.
Immunicin Maymo ont été comparées à to overcome common infectious diseases. All animals were fed, housed, and handled
l’aide d’une analyse de variance univariée Many categories of immunomodulators with due concern for their welfare. The
(ANOVA), avec un seuil significatif have been investigated in animals, but three facilities operated under the guide-
établi à .05. Dans les trois systèmes de only a few have been licensed for use in lines of the animal care and use com-
production, la mortalité chez les finisseurs food animals, both in the United States mittee of the Universidad Autónoma de
et le pourcentage d’animaux réformés and Europe.5 However, this is an active Barcelona. No specific authorization was
étaient plus faibles et les paramètres de field of research, not only with the goals of required for this study as Inmunicin is an
production étaient meilleurs lorsque enhancing survival and clinical parameters authorized product in Spain (ie, it is not an
l’immunomodulateur était appliqué. Les for common infectious diseases, but also for experimental ­product).
différences étaient statistiquement signifi- improving the response to vaccines in many
catives pour tous les paramètres évalués, species.6-12 Use of immunomodulators as Production System ­One
sauf le taux de conversion alimentaire, en an alternative to antibiotic use in livestock is This 7000-sow multi-site production
utilisant les critères SPC dans les Systèmes highly supported by the European Commis- system included nine sow farms. Pig flow
Un et Deux et une ANOVA univariée dans sion’s Seventh Framework Programme for is shown in Figure 1. Briefly, pigs born in
le Système Trois. Les phytostérols pour- research and technical ­development.13 different sow farms were weaned at 21 days
raient être utiles pour maîtriser les PRDC of age and moved to nurseries (Site 2) that
Use of immunomodulators might be a use-
endémiques dans des conditions de terrain. were multi-origin by site and single origin by
ful approach to enhance immune responses
after vaccination with PRRSV modified live room. Nurseries were managed all-in, all-out
vaccines or to overcome infectious diseases by room. Pigs moved from the nurseries to

P
orcine respiratory disease complex in swine. Recently, Inmunicin Maymo the finishing units (Site 3) at 8 to 10 weeks
(PRDC) seems to have evolved with (Maymo Laboratories SA, Barcelona, Spain), of age. Finisher buildings 1, 6, 8, and 9
modern swine production. It is char- a product containing plant phytosterols with were single-origin ie, housed only pigs
acterized clinically by dyspnea, coughing, immunomodulating activity,14 has become from sow farms 1, 6, 8, and 9, respectively.
acute depression, anorexia, fever, and nasal commercially available in Spain. Its exact Finisher buildings 2, 3, 4, 5, and 7 were
discharge, most often affecting growing to composition is protected under European pat- multi-origin, with pigs from two to three
finishing pigs.1 The interaction of multiple ent, but the main component is beta-sitosterol farms of origin per building. All finisher
factors contributes to PRDC. Both viral (BSS). In animals, BSS and its glucoside have buildings were managed all-in, all-out and
and bacterial organisms play a role, as well exhibited anti-inflammatory, antineoplastic, housed approximately 1000 pigs each.
as environmental conditions and various antipyretic, and immune-modulating activ- During 2005, this system experienced
management practices. In the right com- ity15 in a number of studies, including in vitro > 10% mortality in late nursery pigs, early
bination, these factors can compromise studies, animal models, and human clinical finishing pigs, or both, despite treatment
respiratory defense mechanisms sufficiently trials.16 This phytosterol complex seems to with broad-spectrum antibiotics in feed
to cause severe respiratory ­disease.2 target specific T-helper lymphocytes, increas- and water and by injection (data from
The most common viral pathogens associ- ing Th1 activity and resulting in improved 108,000 pigs). During 2006, clinical signs
ated with PRDC are porcine reproductive T-lymphocyte and natural killer cell activity.17 compatible with PRDC were less severe
and respiratory syndrome virus (PRRSV), Taking into account the pathogenic mecha- and mortality decreased, but data from
swine influenza virus (SIV), and porcine nisms of PRRSV, SIV, and PCV2 infections, 120,000 pigs compared unfavorably with
circovirus type 2 (PCV2).3 The most it is possible that an increase in Th1 activity average finisher mortality for pigs in Spain
commonly associated bacterial pathogens would improve the immune response, help- (6.1%) during the same year (J. Font, SIP
include Mycoplasma hyopneumoniae, Acti- ing to minimize the negative production Consultors, oral communication, 2007).
nobacillus pleuropneumoniae, Bordetella consequences in herds where PRDC occurs Both in 2005 and 2006, clinical signs com-
bronchiseptica, Pasteurella multocida, Hae- ­endemically.18-20 patible with PRDC were observed in pigs 8
mophilus parasuis, and Streptococcus ­suis. to 9 weeks of age. For this reason, the com-
Porcine respiratory disease complex causes
pany decided to use Inmunicin Maymo to
Measures used to cope with PRDC include immune dysfunction in affected animals,
improve performance in the system. This
strict management policies, environmental interfering with the capacity to overcome
product was administered to pigs 4 to 12
monitoring, pig flow changes, implemen- infectious challenges.21 Our laboratory has weeks of age (end of the nursery period
tation of strategic vaccination programs preliminary experimental data on the use to the early finishing period) beginning in
focused mainly on viral infectious agents of a phytosterol mixture administered to March 2006. Pigs in finishing closeouts
(PRRSV, PCV2, and SIV), and antibiotic pigs in feed to treat respiratory diseases that beginning in August 2006 received this
medication.4 Antibiotics are used as pre- cause immune dysfunction.22 This case treatment (data for 120,000 ­pigs).
vention, therapeutic treatment, or both in study describes growth-production results
swine medicine. This use has been associ- in three production systems when phytos- Production System ­Two
ated with a significant increase in the resis- terols were administered in feed during the This multi-site production system included
tance pattern of some microorganisms to period when herd records showed that an 1000 sows in a 3-week batch system. Pigs
antibiotics used in human and veterinary outbreak of PRDC was likely to ­occur. were moved to a nursery at a weaning age
medicine.4 For this reason, many alterna-
of 21 days. The nursery was single-origin by
tives to antibiotic use have been considered Production ­systems site, single-aged by room, and managed all-
by the swine industry, including natural The three pig-production systems in, all-out by room. The finishing units were
substances (immunomodulators) that may described in this study belonged to two filled with pigs from this nursery (9 weeks
Journal of Swine Health and Production — Volume 17, Number 1 33
 Figure 1: Pig flow for Production System One, a 7000-sow multi-site system in Spain. Finisher buildings 1, 6, 8, and 9
housed only pigs from sow farms 1, 6, 8, and 9, respectively. Finisher buildings 2, 3, 4, 5, and 7 each housed pigs from two to
three farms of origin. Numbers in parentheses represent additional sow farms of origin. All finisher buildings were man-
aged all-in, all-out (approximately 1000 pigs per ­barn).

Sow farms
(Site 1)
1 2 3 4 5 6 7 8 9

Nurseries single origin by room and multi-origin by building

Nursery phase
(Site 2) 1 2 3 4 5 6 7 8 9

Finishers single origin by room and single or multi-origin by building

Finisher phase
(Site 3)
1 2 (1) 3 (5,6) 4 (1,3) 5 (7,8) 6 7 (5,6) 8 9

of age) and were managed all-in, all-out by During 2006, the system experienced high Parameters ­evaluated
building (between 1000 and 1500 pigs per mortality in the finishing period because Criteria evaluated included average daily
barn). Each closeout was from one finisher of PRRS outbreaks in some sow farms. gain (ADG), feed efficiency, mortality, and
­barn. Clinical signs characteristic of PRDC were percent culls during the finisher phase.
observed when pigs were 13 weeks of age. Average daily gain was calculated as the
During 2005, the system experienced > 10%
The company decided to use Inmunicin difference between final weight at closeout
mortality in the finishing period (data from
Maymo to improve performance, with treat- and initial weight of all pigs, divided by the
21,589 pigs in 21 barns) and clinical signs
compatible with PRDC were observed when ment administered to pigs 9 to 17 weeks of length of the finisher period. Mortality was
pigs were 13 weeks of age. Mortality did not age in some finisher batches beginning in calculated as the number of pigs that had
improve significantly during 2006 (data June 2006. Others batches were not treated died by closeout divided by the number of
from 11,922 pigs in eight barns). For this (controls). Control and treated batches orig- pigs that had entered the finisher. Percent
reason, the company decided to use Inmu- inating from the same sow herd included culls was calculated as the number of culls
nicin Maymo to improve performance in closeouts of 28,252 and 12,902 pigs from at closeout divided by the number of pigs
pigs 9 to 17 weeks of age, with treatment 10 and four finisher farms, ­respectively. that had entered the finisher. Feed effi-
beginning in January 2006. Pigs in finish- ciency was calculated by dividing feed con-
sumption (including feed wastage) at barn
ing closeouts beginning in May 2006 Treatment with Inmunicin level during the finisher period by the dif-
(batch 29) received this treatment (data ­Maymo ference between final weight at closeout and
from 16,694 pigs in 14 ­barns). In each production system, Inmunicin initial weight of all pigs that had entered the
Maymo was administered according to finisher in the three production ­systems.
Production System ­Three the label instructions (2 kg of Inmunicin
This 2135-sow multi-site production sys- Maymo per tonne of feed) during the Diagnostic ­testing
tem included three farms, with 500 to 900 Diagnostic testing was performed in each
period from 4 weeks before until 4 weeks
sows per farm. Pigs born in different sow production system at several time points.
after the predicted date of a PRDC out-
farms were moved to nurseries (Site 2) at Blood samples from 12 animals that
break, according to clinical experience in
a weaning age of 21 days. Nurseries were exhibited signs of PRDC (dyspnea, cough-
that system. No changes in gilt acclima-
multi-origin by site and single origin by ing, anorexia, and fever) were collected
room, and were managed all-in, all-out by tion, genetic background, vaccinations,
semen extenders, boar management, or and tested for PRRSV genomes by reverse
room. The finishing units (1350 to 4220 transcriptase polymerase chain reaction (RT-
pigs per barn) were filled with pigs from weaning age of pigs were made during the
treatment ­period. PCR).23 Samples were collected on the day
these nurseries (8 to 10 weeks of age) and when clinical signs were first noticed (Day
were managed all-in, all-out by ­building. 0) and from the same ear-tagged animals 21
34 Journal of Swine Health and Production — January and February 2009
days later (Day 21). Extraction and amplifi- upper control limit, and lower control limit Mortality, percent culls, and
cation of PRRSV DNA was performed on were calculated from the inherent variation production ­parameters
pools of Day 0 samples (four samples per using the software described. The chart was The mean values of the studied parameters
pool). Day 0 and Day 21 sera were tested selected according to the type of analyzed in Systems One and Two are represented in
for PRRSV antibodies by ELISA (Herd- data and whether or not the data was nor- the XmedianR charts (Figures 2, 3, 4, and
Chek PRRS 2XR; Idexx Laboratories, mally ­distributed.25 5). This chart was chosen because the mean
Barcelona, ­Spain). values for the studied parameters were
Production parameters (ADG, feed normally distributed (NCSS 2004 and
Necropsies were performed by the herd efficiency, and mortality) of control and PASS 2005 software). From these mean
veterinarian during the PRDC outbreak. To treated batches in System Three were values, in both production systems, three
avoid misinterpretation of pathological find- compared in a one-way ANOVA, as data periods could be clearly defined: Unstable,
ings, only fresh specimens (ie, no autolyzed for controls and treated groups were gener- Stable, and Stable with immunomodula-
carcasses) were examined. The main purpose ated concurrently rather than in successive tor. The dates of the beginning and end of
of necropsy was to determine whether or groups as in Systems One and Two. Level each period are shown in Table 2. Highest
not postweaning multisystemic wasting syn- of significance was established at < .05. All mortality and percent culls and worst
drome (PMWS) was a significant contribu- analyses were performed in NCSS 2004 production parameters were observed
tor to disease and mortality. Tissue samples and PASS 2005 (NCSS, Kavysville, ­Utah). during the first period (Unstable) in both
(lung, superficial inguinal lymph node, production systems, which corresponded
spleen, kidney, and liver) were submitted to Results of diagnostic ­testing with the epidemic phase of PRRS, PMWS,
the histopathology department, Universidad Diagnostic results are described in Table 1. or both in each production system. In both
Autonoma de Barcelona (Barcelona, Spain), Infections with both PRRSV and PCV2 systems, the outbreak of PRDC was first
for histopathology and testing for PCV2 were diagnosed in System One, while noticed during this period, and treatment
infection by in situ ­hybridization.24 PMWS alone was diagnosed in System with antimicrobials began. It was not pos-
sible to calculate chart limit values during
No microbiological isolation was Two and PRRS alone was diagnosed
the Unstable period, because SPC may be
attempted, as many animals were being in System Three on a single occasion.
applied only in a stable situation.26 During
treated with antimicrobials prophylactically Diagnostic testing for PMWS was not
the following period (Stable), all studied
or therapeutically during the PRDC out- performed in System Three. In Production parameters ­improved.
break. Pigs were treated with tiamulin (200 Systems One and Two there was a clinical
diagnosis of PRDC (respiratory signs as This stable phase was associated with the
g per tonne) and chlortetracycline (400
described) and a laboratory diagnosis of endemic phase of PRRS, PMWS, or both,
g per tonne) in the feed at the end of the
PRRSV infection, PCV2 infection, or both but production parameters were always
nursery period and early in the finishing
during the Unstable, Stable, and Stable inferior to those accepted as average in
period (5 weeks ­total).
with immunomodulator periods (defined Spain (J. Font, SIP consultors [[Link]-
in Table 2 and described in Figure 2). No [Link]], oral communication,
Statistical ­analyses additional diagnostic testing was performed 2007). During the stable period, natural
Data from Systems One and Two were variation inherent in a process is expected
for other ­pathogens.
incorporated into a database program and
analyzed using statistical process control
(SPC) techniques25 to assess changes in Table 1: Results of diagnostic testing for two agents associated with porcine
performance before and after addition of respiratory disease complex in finisher pigs in three production systems in Spain
the immunomodulator to the feed. If the
process remained in control, future mea- PRRSV*
surements would continue to follow the Production system PCR-positive Seroconversion PMWS †
same probability distribution as previously.
One Yes Yes Yes
All analyses were performed with the QI
Macros2007 SPC for Excel (KnowWare Two No No Yes
international Inc; [Link]-spc-soft- Three Yes Yes ND
[Link]/[Link]).
System changes were considered significant * Blood samples were collected from the same 12 animals on Day 0 (first observation
if one or several of the following conditions of dyspnea, coughing, anorexia, and fever) and Day 21. Day 0 samples were tested
existed: one single point more than 3 s for PRRSV by reverse-transcriptase PCR. Day 0, and Day 21 samples were tested
away from the mean; at least two of three for PRRSV antibodies by ELISA (HerdChek PRRS 2XR; Idexx Laboratories, Barcelona,
Spain), defining a positive result as sample:positive ratio (S:P) > 0.4. Seroconversion
successive points 2 s away and on the same was defined as an S:P in the Day 21 sample that was at least three times that of the
side of the mean; at least nine successive Day 0 sample.
points on the same side of the mean; at † PMWS was diagnosed using fresh specimens and internationally accepted criteria19
least four of five successive points 1 s away for clinical signs and histopathology lesions, and porcine circovirus type 2 was
and on the same side of the ­mean. detected by in situ hybridization.
PRRSV = porcine reproductive and respiratory syndrome virus; PCR = polymerase
A control chart was constructed for each chain reaction; PMWS = postweaning multisystemic wasting syndrome;
analyzed parameter and the control limit, ND = not done.
Journal of Swine Health and Production — Volume 17, Number 1 35
 Table 2: Beginning and ending dates for periods when parameters analyzed using statistical process control methods
were clearly different in two production systems with endemic PRDC treated by administration of an immunomodulator*

Period of time Beginning date End date

System One
Unstable January 2005 September 2005
Stable October 2005 July 2006
Stable with immunomodulator August 2006 June 2007
System Two
Unstable January 2005 (Batch 1) August 2005 (Batch 13)
Stable September 2005 (Batch 14) May 2006 (Batch 29)
Stable with immunomodulator May 2006 (Batch 30) January 2007 (Batch 43)

* The Unstable time period corresponds to an outbreak of PRDC (epidemic phase of PRRS, PCV2, or both), when the highest levels of
mortality and percent culls, and worst production parameters, were observed, and treatment with antimicrobials began. The Stable
period was associated with the endemic phase of PRRS, PCV2, or both. During the third period (Stable with immunomodulator), 4
weeks before until 4 weeks after the predicted date of a PRDC outbreak, the immunomodulator Inmunicin Maymo (Maymo Laborato-
ries SA, Barcelona, Spain) was administered (2 kg per tonne of feed).
PRDC = porcine respiratory disease complex; PRRS = porcine reproductive and respiratory syndrome; PCV2 = porcine circovirus type 2.

Figure 2: Finisher mortality in Production System One. Each monthly average represents closeouts of 12 finisher barns
(approximately 1000 pigs per barn). Unstable, Stable, and Stable with immunolmodulator periods described and defined in
Table 2. The blue line represents the average value for finisher mortality in pigs in Spain (J. Font, SIP Consultors, oral
communication, 2007).

16

14

12
Finisher mortality (%)

10

0
Ap

Ap
No

No

Ap
Au

Au
Oc

Sp
Oc
Ma

Ma

Ma

Ma

Ma

Ma
Dc

Dc
Sp
Fe

Fe
Jn

Fe

Jn
Ja

Ja

Ja
Jn
Jl

Jl

2005 2006 2007

Year

36 Journal of Swine Health and Production — January and February 2009

 Figure 3: Percent culls in Production System One (described in Figure 1). Each monthly average represents closeouts of 12
finisher barns (12,000 pigs). Unstable, Stable, and Stable with immunomodulator periods are described in Figure ­2.

4
Culls (%)

No
No
Ap

Ap

Ap
Au

Au

Oc
Oc
Ma

Ma

Ma

Ma

Ma

Ma
Dc

Dc
Sp

Sp
Fe

Fe

Fe
Jn
Ja

Ja
Jn

Jn
Ja
Jl
Jl

2005 2006 2007

Year

to occur according to the underlying statis- plants. Many categories of immunomodula- compare the performance of a process by
tical distribution. Production parameters in tors have been investigated in food-producing using statistical process control to examine
both production systems were best during animals, but only a few have been licensed data collected before and after a change has
the period when the immunomodulator was for use in food animals by regulatory authori- been introduced. This tool has been widely
administered (Figures 2, 3, 4, and 5). More- ties, not only in the United States, but also used in pig production to assess the efficacy
over, in both production systems, according in Europe. Many authorized products were of vaccine protocols and feed additives
to SPC criteria, the changes in the system licensed after clinical studies demonstrated under field conditions, where formal stud-
were statistically significant for all param- efficacy of the products by measuring improve- ies (using concurrent control and treated
eters except feed efficiency (Table 3). ments in clinical or production parameters groups) were not ­suitable.30-32
or both.27 In the three production systems
System Three experienced high mortality in Immunomodulators licenced in Europe for
described in this study, growth-production
the finisher during 2006 because of PRRS use in swine are usually administered by
parameters, mortality, and percent culls were
outbreaks in some sow farms. The immu- the parenteral route, either alone or com-
examined to assess whether a phytosterol
nomodulator was administered to pigs from bined with vaccines.33-35 However, when
mixture administered in the feed could aid
9 to 17 weeks of age in some batches, and the objective is to administer a product to
in control of endemic PRDC under field
other batches were not treated. Lower mor- a large population, the oral route is much
­conditions.
tality and better production parameters were more practical. For this reason, it is very easy
observed in the group treated with the immu- Formal studies are designed to determine to understand that nutraceuticals are the
nomodulator (Table 4). These differences the efficacy of a product to treat a disease fastest growing category of immunomodula-
were statistically significant (P < .05) for all or disease complex. These studies are usu- tors.5 A nutraceutical is a food that provides
studied parameters except feed ­efficiency. ally performed using a small number of medical or health benefits, including pre-
animals under experimental conditions. vention or treatment of disease.36 The oral
Extrapolation of results to practical situa-
Discussion tions has been extensively discussed.28,29
route has been used to administer immu-
The objective of immunomodulation in nomodulators to fish. For example, Kumari
Using a formal study with concurrent and Sahoo8 showed that the introduction
food-producing animals is to control an control and treated groups, Pearson et
immune response for the benefit of the of β-1,3 glucan, levamisole, lactoferrin, and
al10 showed that low-dose dietary supple- vitamin C (pharmaceutical and nutraceuti-
animal and for production efficiency. mentation with ginseng (a traditional
Substances that exert this control are called cal immunomodulators) into the diet of fish
medicinal plant) may be a useful adjunct
immunomodulators.5 Broad categories of grown in farms under immunosuppressive
to vaccination against equid herpesvirus
immunomodulators include cytokines, or stressful conditions enhances protection
1 in horses. A simpler approach than a
pharmaceuticals, microbial products, against infection and offers economic
formal trial may be performed under field
nutraceuticals, and traditional medicinal ­benefits.
conditions. For example, it is possible to
Journal of Swine Health and Production — Volume 17, Number 1 37
 Figure 4: Finisher mortality in Production System Two, a 1000-sow multi-site system working in a 3-week batch system.
Each closeout is from one finisher barn (1000 to 1500 pigs per barn). The Unstable (data from 21 barns), Stable (data from 8
barns), and Stable with immunomodulator (data from 14 barns) periods are described in Figure 2. The blue line represents
the average value for finisher mortality in pigs in Spain (J. Font, SIP Consultors, oral communication, ­2007).

16

14

12
Finisher mortality (%)

10

31

34

37

40
1

10

13

16

19

22

25

28
Batch

The mechanisms of action of phytosterols is involved in protection of mice against standard diet. These results suggest that
in swine remain elusive. Few reports in disseminated candidiasis. In this disease, immunomodulation was apparent not only
the literature describe the mechanisms of the dominance of Th2 responses correlates 2 days after vaccination with a PRRS MLV
action of immunomodulators. Schierack with severity of the fungal infection, and (innate phase of the immune response),
et al11 showed that feed supplementation Th1-type dominance can reduce severity.39 but also during the acquired phase of the
with the probiotic Bacillus cereus var toyoi Unpublished data from our laboratory immune response such that these responses
(a microbial product) improved the out- agree with these results, showing that beta- might aid in control of infectious diseases
come of vaccination against Mycoplasma sitosterol treatment enhanced immune that contribute to ­PRDC.22
hyopneumoniae and influenza virus by responses in pigs. Lymphocyte function,
In this study, lower finisher mortality and
modulating the composition and activities assessed as ability to proliferate in the percent culls and the best production
of blood immune cells in treated piglets. presence of different concentrations of parameters were observed in all three pro-
Data reported by Yuk et al37 suggest that phytohemagglutinin (PHA), was measured duction systems when the inmunomodula-
beta-sitosterol, the main component of in porcine blood mononuclear cells 2 days tor was applied. These system changes were
Inmunicin Maymo, may be a potential after vaccination with an MLV PRRS vac- statistically significant for all parameters
therapeutic molecule in asthma because in cine. Surprisingly, PRRS MLV vaccination except feed efficiency, according to SPC
this respiratory disease, Th1/Th2 balance induced a decrease in PHA proliferation criteria for Systems One and Two and
is switched towards Th2 (antibody pro- responses during the first 2 days after vac- ANOVA criteria for System Three. Feed
duction).38 Beta-sitosterol seems to target cination in animals fed a standard diet. In efficiency depends on feed consumption and
specific T-helper lymphocytes, increasing contrast, when treatment with Inmunicin weight gain during a period of time. The
Th1 activity and resulting in improved T- Maymo was administered in the diet, PHA mortality observed in Systems One and Two
lymphocyte and natural killer cell activity proliferation responses were normal. In occurred during the first month of the fin-
(cellular immunity).17 Recently, Lee et al39 addition, when IL-6 levels were measured isher phase, so the impact on feed efficiency
showed that daucosterol, a beta-sitosterol to evaluate tissue damage during the might be minimal, as observed in this ­case.
glycoside, has an immunomodulating acquired phase of the immune response, It can be argued that the observed improve-
activity that mediates induction of Th1- 33 days post administration of the PRRS ment in most of the studied parameters
dominant cytokine production from MLV vaccine, levels were generally lower during the third period in Systems One and
activated CD4+ T-cells. This Th-1 response in pigs fed phytosterols than in pigs fed a Two is a direct consequence of the natural
38 Journal of Swine Health and Production — January and February 2009
 Figure 5: Average daily gain (ADG) in Production System Two. The Unstable (data from 21 barns), Stable (data from 8
barns), and Stable with immunomodulator (data from 14 barns) periods are described in Table 2. Each value is calculated
from closeouts of each finisher barn (1000 to 1500 pigs per ­barn).

800

750

700

650

600
ADG (g)

550

500

450

400

31
13

22
10

16

25

34
1

19

28

37

40
Batch

Table 3: Chart limits for two production systems in Spain* calculated applying statistical process control

Period 2 (Stable)† Period 3 (Stable with immunomodulator)†

Parameter Control limit Upper control Lower control Control limit Upper control Lower control
limit limit limit limit
Production System One
Culls (%)‡ 2.5 4.9 0.2 1.9 3.0 0.7
Feed efficiency§ 2.68 2.84 2.52 2.63 2.71 2.55
Mortality (%)¶ 6.7 8.2 5.2 4.9 6.9 2.9
Production System Two
ADG (g/day)** 632.3 705.0 559.4 706.0 745.0 666.4
Feed efficiency§ 2.55 2.77 2.32 2.42 2.52 2.32
Mortality (%)¶ 7.1 10.0 4.2 3.7 6.6 0.8

* Production System One (described in Figure 1) and Production System Two in which endemic porcine respiratory disease complex
was treated by administration of an immunomodulator. In Production System Two, nurseries were single-origin by site and managed
all-in, all-out, and finishing units were filled from a single nursery and managed all-in, all-out by building. Average daily gain (ADG) for
System One and percent culls for System Two were not analyzed because of missing values.
† Process control periods described in Figure 2.
‡ Percent culls = (number of culls at closeout ÷ number of pigs that entered the finisher) × 100.
§ Feed efficiency at barn level = feed consumption during the finishing period ÷ (final weight of all pigs at closeout – initial weight of
all pigs that entered the finisher).
¶ Mortality = (number of dead pigs at closeout ÷ number of pigs that entered the finisher) × 100.
** Average daily gain (ADG) = (final weight of all pigs at closeout -- initial weight of all pigs that entered the finisher) ÷ length of the
finishing period.
Journal of Swine Health and Production — Volume 17, Number 1 39
 12. Shan T, Wang Y, Wang J, Liu J, Xu Z. Effect
Table 4: Means (± standard deviation) for ADG, feed efficiency, and mortality of lactoferrin on the immune functions and
in Production System Three for batches of finishers either treated with an serum iron level of weanling piglets. J Anim Sci.
immunomodulator* or not treated (Controls) ­2007;85:2140–2146.
13. Seventh Framework Programme for research
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ADG (g/day)‡ 601.6 (43.6) 664.7 (29.8) < .05
14. Bouic PJD. The role of phytosterols and phy-
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*15. Lamprecht JH. A comparison of the survival
* Inmunicin Maymo (Maymo Laboratories SA, Barcelona, Spain) administered in benefit provided by putative immune modula-
feed to pigs 9 to 17 weeks of age in some finisher batches beginning in June 2006. tors in the FIV (feline immunodeficiency virus)
Control and treated batches originating from the same sow herd included closeouts infected laboratory cat model. Proc 13th Int AIDS
of 28,252 and 12,902 pigs from 10 and four finisher farms, respectively. Conf. Durban, South Africa. ­2000;21–24.
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Flow cytometric analysis of the Th1-Th2 balance
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pigs that entered the finisher) ÷ length of the finishing period. the human immunodeficiency virus (HIV) receiv-
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Journal of Swine Health and Production — Volume 17, Number 1 41

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