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Vaccination against Streptococcus suis:
Effect on nursery mortality
Montserrat Torremorell, DVM; Carlos Pijoan, DVM, PhD; Emilio Trigo,
DVM, PhD
Copyright (C) 1997 American Association of Swine Practitioners
Also available in PDF format.
Summary
Purpose: To evaluate the effect of selected vaccines and administration
routes on mortality of nursery pigs due to Streptococcus suis.
Methods: A field trial was conducted on one group of nursery pigs
(N=330). Pigs were randomly allocated to one of four groups that each received
one of the following treatments at weaning: an experimental autogenous vaccine
administered intramuscularly (IM) (n=90); a standard autogenous vaccine
administered IM (n=90); a commercial bacterin, administered intraperitoneally
(IP) (n=60); or no vaccine (n=90). Nursery mortality was monitored from
the start of the trial (18 days of age) until the end of the nursery period
(9 weeks of age).
Results: Nursery mortality before the start of the trial was approximately
17%. There were no significant differences among the four treatment groups;
however, there was a trend toward decreased mortality among pigs that received
the experimental autogenous vaccine. Overall nursery mortality at the end
of the trial had decreased to 3.3%. Following the trial, an IP vaccination
protocol with the commercial bacterin was initiated among all nursery pigs
for 6 months. Total nursery mortality while this protocol was in place was
3.48% (SD=1.45) and the mortality rate for pigs that showed CNS signs at
the time of death was 2.55% (SD=1.2). After this 6-month vaccination program,
the owner of the herd switched to a sow vaccination strategy with the commercial
bacterin. For the 6 months during which the sow vaccination protocol was
monitored, total nursery mortality was 2.66% (SD=1.65), with mortality of
pigs demonstrating terminal CNS signs at 2.0% (SD=1.61).
Implications: Vaccination does not totally control S. suis
Keywords:
Streptococcus
suis, vaccine,
mortality
Received: Jan 28, 1997
Accepted: May 9, 1997
Meningitis caused by Streptococcus suis is
becoming a more severe and uncontrollable problem in the United States swine
industry. Nursery pigs are the most commonly affected, but outbreaks in
finishing pigs have also been reported.1 Mortality rates of 4%-5%
are common, and can increase to 15%. It is not clear why S. suis infections
are increasing in prevalence, but it could be associated with:
- early weaning systems, in which pigs are weaned at <=18 days of
age,2
- herds that have recently enlarged their sow inventory, and
- concurrent infections that may be present in the herd, such as porcine
respiratory and reproductive virus (PRRSV).3
Different measures to control meningitis--including intensive antibiotic
treatments and/or vaccination of the piglets or the sows--have been attempted,
but have not been successful.4 Several commercial and autogenous
S. suis vaccines are available, but their field effectiveness has
not been reported. Although they do not seem to achieve total control of
the problem, vaccine use has been reported to decrease mortality to more
manageable levels.5
Previous work has suggested that the early stages in the pathogenesis
of S. suis may involve dissemination of the bacteria surviving within
macrophages.6 This suggests that protection may depend on stimulating
cellular immunity--something that is unlikely to happen with killed vaccines
using conventional adjuvants and injection routes.7,8 The IP
route has been reported to give better stimulation of both humoral and cellular
immune responses.8 This paper reports our study of the effects
of oil-adjuvanted IP vaccination against S. suis.
Material and methods
Herd history and clinical evaluation
In October 1995, the owners of a commercial swine herd contacted the
University of Minnesota and reported high levels of nursery mortality (Figure 1). This herd was established
at the beginning of 1994, but its target sow inventory (975 sows) was not
reached until mid-1995. The herd was a two-site production unit with farrowing
and nursery rooms at one site and finishers at another site. The average
weaning age was 15 days, with preweaning mortality of 11% and average sow
parity of 2.0. Replacement gilts were selected from the finishing herd and
only boars were purchased from outside.
The herd had elevated nursery mortality rates in September 1995 that
reached 17%. All affected pigs showed signs of meningitis, arthritis, or
a combination of these signs. Streptococcus suis serotype 2 was isolated
from the brain samples of 12 necropsied pigs submitted at different times
to a diagnostic laboratory. Most of the mortality occurred between 3 and
7 weeks after weaning. Clinically affected pigs were injected with ampicillin
and/or ceftiofur sodium and put into a sick pen.
During the course of the present study, this herd was concurrently infected
with PRRSV and transmissible gastroenteritis virus (TGEV). A clinical PRRSV
outbreak was observed in January 1996, but serology performed in March 1995
had already shown some seropositive pigs. A TGEV outbreak was clinically
observed in March 1996 and affected mostly baby and nursery pigs, but no
virus isolation was performed.
Field vaccine trial
In consultation with the herd owner, a S. suis vaccination program
was initiated in November 1995. Because the literature reports inconsistent
findings regarding the efficacy of the S. suis vaccines,4,5,9
we performed a concurrent controlled study in the herd with pigs from only
1 week of production.
One weekly group (330 pigs) of 15-day-old pigs was randomly distributed
into four experimental groups, and allocated to a 12-pen room at weaning.
Each pen housed 30 pigs, with one empty pen used as a sick pen. All pigs
were housed in the same room, but pens had solid partitions between them
and no pigs were moved other than to house them in the sick pen at one end
of the same room. Each treatment group (three pens of 30 pigs each) received
one of the following treatments:
- An experimental autogenous vaccine prepared in our laboratory using
the S. suis serotype 2 isolated from the brain of a neurologically
affected pig in the herd (n=90). This vaccine had an oilin-water adjuvant
(Imugen(R), Bayer Animal Health, Worthington, Minnesota), adjusted
at 4x108 CFU per mL, inactivated with 0.2% formaldehyde, and
administered intraperitoneally (IP).
- An autogenous vaccine that was commercially prepared with a serotype-2
isolate recovered from brain tissue from the herd 10 months previous to
the trial (n=90). It had an aluminium hydroxide adjuvant and was administered
intramuscularly (IM).
- A commercial bacterin prepared with a serotype-2 strain, oil-in-water
adjuvant, administered IP (manufacturer recommendations suggest IM administration)
(n=60).
- nonvaccinated controls (n=90).
Pigs were vaccinated at weaning and revaccinated 10 days later. Pigs
with signs of meningitis and/or arthritis were placed in the sick pen and
injected with ampicillin (6-8 mg per kg) or ceftiofur sodium (3-5 mg per
kg). Morbidity and mortality rate was monitored from the beginning of the
trial (at weaning) until the pigs left the nursery (at 9 weeks of age).
Statistical analysis
Differences in morbidity and mortality between groups were statistically
analyzed using the c-square test. Groups were considered to be statistically
significant at P<.05.
Posttrial vaccination protocols
Following this controlled trial, the producer adopted a new vaccination
protocol that was designed to boost the immune response and protect pigs
with different levels of maternal immunity. Starting in late November 1995,
piglets were vaccinated with the commercial bacterin IP at 5 days of age,
revaccinated IP at weaning (15 days of age), and revaccinated again 10 days
later IM. This program was followed in the herd for 6 months.
A TGEV outbreak in March 1996 convinced the producer to begin attempts
to determine the causes of nursery pig mortality. Thus, after March 1996,
the herd records differentiated between total mortality data of pigs and
mortality that could be directly attributed to S. suis (i.e., pigs
that exhibited obvious CNS distress, ataxia, tremors, and paddling).
In May 1996, the producer decided to adopt a sow vaccination protocol,
which was less expensive, less time consuming, and easier to implement.
Sows were vaccinated IM with the commercial bacterin at approximately days
77 and 98 of gestation. Piglets were followed during the nursery stage,
and mortality rates were used to evaluate the effectiveness of this protocol.
This protocol was still in use at the time of this report.
Results
Pigs that received the experimental autogenous vaccine tended to have
lower morbidity/mortality (P<.1) than pigs in the other groups
(Figure 2). Mortality in the
nonvaccinated group was 5.5 % and morbidity was 13%; both were lower than
the 17% mortality observed in groups of weaned pigs in the herd previous
to the on-farm vaccine trial. Mortality was nonexistent among pigs vaccinated
with the commercial vaccine during the first 4 weeks of the experiment,
but increased to 10% during the last 2 weeks of the trial.
In comparison, mortality rate was 14% for a nearly identical group of
pigs that was not vaccinated and that received identical diet and management
and was weaned within 1 week of the pigs included in the trial. These pigs
were housed in an adjacent room to those included in the trial, and shared
the same airspace.
After the trial, when the IP vaccination protocol was initiated for all
nursery pigs in the herd (n=22 weekly groups), mortality for the nursery
pigs averaged 3.48% (SD=1.45) and the average mortality of pigs exhibiting
terminal CNS signs was 2.55% (SD=1.2). Pigs showed inappetance for 1 day
after vaccination. In addition, small (approximately 2 mm in diameter) focal
lesions of peritonitis were observed in some of the nursery pigs that died
during the nursery stage. These lesions had not been observed during the
previous experimental vaccination trial, in which the IP vaccination was
performed on older pigs. None of the nursery pigs that received the IP commercial
bacterin subsequent to the field trial were condemned at slaughter, suggesting
that the lesions had either resolved or were not significant.
Total mortality of nursery pigs during the sow vaccination protocol was
2.66% (SD=1.65) (n=26 weekly groups of pigs) and mortality of the pigs that
died with terminal CNS signs was 2.0% (SD=1.61) (n=26 weekly groups of pigs).
Discussion
It is always difficult to assess observations made in field trials, because
there are many uncontrolled factors in commercial herds that can influence
the results. Therefore, the effect of vaccination in reducing mortality
of nursery pigs attributable to S. suis in this trial cannot be definitively
assessed. It is tempting to attribute the decrease in mortality rates to
the vaccine, but because other factors in the herd--which might have had
effects on mortality--were not controlled, it is impossible to make definite
conclusions about the role of vaccine in this herd.
Nursery mortalities were already decreasing at the time the experiment
was begun (Figure 1). The fact
that mortality for the trial pigs was lower than both the previous and succeeding
groups of pigs from that nursery room suggest that the vaccine may have
been somewhat efficacious in reducing morbidity and mortality due to S.
suis in this herd. The nonvaccinated group that served as a control
in the field trial had lower morbidity and mortality than expected based
on previous morbidity and mortality rates in the herd. If the morbidity
and mortality rates for the nonvaccinated controls had remained at 17%,
the difference between this group and vaccinated groups would probably be
statistically significant. The reduced morbidity and mortality rates observed
in the nonvaccinated control pigs is not uncommon in field trials and could
be attributable to decreased challenge exposure from the vaccinated pigs
in the same room.
Because the role of maternal immunity in S. suis infections is
unknown and because we can only estimate when colonization by the virulent
strain occurs,10 we decided to be conservative and vaccinate
the piglets IP at 5 days of age, with revaccination at weaning and 10 days
later. This extensive vaccination protocol was designed to give increased
coverage to those pigs that might be receiving the first vaccine dose while
still under maternal protection.
Mortality was being kept at reasonable levels when the outbreak of TGEV
took place (May 1996). This outbreak also shows that even though the herd
was a two-site, high-health facility, its biosecurity was not tight. Nursery
mortalities increased during the TGEV outbreak, making it difficult to differentiate
mortality due to S. suis from mortality caused by the TGEV. During
the outbreak, there were groups with very high mortality (5%) together with
groups with very low mortality (1.4%). It is not uncommon to observe variability
in the mortality due to S. suis between groups from consecutive weaning
weeks. This is often attributed to variation in the weather, temperature,
or humidity as well as other factors, but no studies have been done to support
this conjecture.11
We observed a decrease in nursery mortality after the sow vaccination
protocol was initiated when the first close-outs of pigs coming from vaccinated
sows were evaluated. It is worth noting that every time a change was implemented
in the herd, an improvement was observed regardless of treatment. However,
after several groups of pigs had gone through after the sow vaccination
protocol was begun, mortality increased again and fluctuated as before.
Both total mortality and CNS mortality were lower after the initiation of
the sow vaccination protocol than the values observed in the vaccination
trial, but the standard deviations were larger, indicating substantial variability.
Although overall mortality was reduced, some groups had mortality rates
as high as 5.8% (Figure 1).
It is unclear why vaccines against S. suis do not, in general,
achieve total control of the disease. It is believed that S. suis
reaches the brain inside monocytes, thus escaping the action of the immune
system.12 Virulent strains of S. suis can survive inside
monocytes and multiply.6 In theory, therefore, antibodies against
S. suis cannot penetrate the cells and inactivate the microorganism.
This would support the idea that stimulating cellular immunity would be
more efficient than stimulating a humoral response to control S. suis
meningitis. However, stimulation of cellular immunity is unlikely to occur
with killed vaccines using conventional adjuvants and injection routes.7
To address this issue, we proposed IP vaccination with an oil-in-water adjuvant
as a possible strategy to stimulate a better response.8 The results
showed that although these vaccines did perform better than the conventional
gel-adjuvanted IM products, they still failed to achieve complete control
of the problem.
Other problems with vaccination against S. suis exist. The level
of cross protection among serotypes is not known, but is believed to be
low.5 Membrane protein or hemolysin preparations have produced
good results experimentally, but when these preparations are used in commercial
herds they do not fully control the problem.9,13,14 Because of
this lack of knowledge about the virulence factors for S. suis, autogenous
vaccines prepared with oil-in-water adjuvants seem to be, at this point,
the best choice since they presumably offer a degree of cellular immune
stimulation. We chose to use a commercial vaccine in the modified IP and
sow vaccination program because the strain involved was a serotype 2, which
is the one commonly used in commercial products.
Implications
- Vaccination against S.suis may help lower nursery mortalities
to more manageable levels; however, this does not always totally solve
the problem.
- Sow vaccination should be evaluated further, since it may give slightly
better results and is less costly and labor intensive.
- The IP injection route should be considered as a possible vaccination
route. However, we observed some undesirable side effects, such as peritonitis,
especially in very young pigs.
- Mortality and morbidity rates in nursery pigs fluctuate regardless
of treatment.
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