Professional Documents
Culture Documents
Abstract
Our aims were to evaluate the published literature concerning the effect of swine vaccination
against Mycoplasma hyopneumoniae on the average daily weight gain (ADWG). This was done by
re-evaluating the in¯uence of selected factors on ADWG by a meta-analysis of published studies
from 1991 to 1999, ful®lling certain inclusion criteria.
With ADWG as the outcome, an analysis of variance was performed for such variables as
treatment, vaccination schedule, age during study, housing system and publication quality. Each
clinical trial was considered as a random effect and the numbers of pigs in each trial were weightings.
Of 63 published studies, 16 describing three commercial vaccines ful®lled the criteria for the meta-
analysis. Due to few studies with one of the vaccines
n 3, only two vaccines were included.
Vaccinated pigs gained an average of 592 g
S:E: 15 with Stellamune1 and 590 g
S:E: 15
with Suvaxyne1 compared to non-vaccinated pigs that gained an average of 569 g
S:E: 14
P < 0:01 when adjusted for age during the study. Vaccine type, vaccination schedule, housing
system and publication quality were not signi®cantly associated with ADWG. # 2002 Elsevier
Science B.V. All rights reserved.
*
Corresponding author. Present address: Department of Clinical Studies, The Royal Veterinary and
Agricultural University, Dyrlñgevej 88, DK-1870 Frederiksberg C, Denmark. Tel.: 45-35-28-28-43;
fax: 45-35-28-28-38.
E-mail address: csj@kvl.dk (C.S. Jensen).
0167-5877/02/$ ± see front matter # 2002 Elsevier Science B.V. All rights reserved.
PII: S 0 1 6 7 - 5 8 7 7 ( 0 2 ) 0 0 0 0 5 - 3
266 C.S. Jensen et al. / Preventive Veterinary Medicine 54 (2002) 265±278
1. Introduction
Swine enzootic pneumonia causes major economic losses in the pig industry world-
wide (Ross, 1999). Mycoplasma hyopneumoniae is the primary agent responsible, but
secondary infections from Actinobacillus pleuropneumoniae, Pasteurella multocida and
Streptococcus suis also can increase the severity of the disease (Christensen et al.,
1999). In Denmark, 6.9 million doses of vaccines against M. hyopneumoniae were sold
in 1998, for an annual production of approximately 2 million pigs (Anon., 1998). Three
different commercial vaccines against M. hyopneumoniae were available in Denmark
in the study period: Stellamune11 (RespiSure1 outside Europe), Suvaxyn12 and
Hyoresp1.3 The vaccines were used to reduce the severity of pneumonia, and thereby
increase productivity by improving the average daily weight gain (ADWG) (Dayalu
et al., 1992; Dayalu, 1994; Nash, 1996). Both the Stellamune1 and Suvaxyn1 vaccines
contain inactivated whole cell cultures of M. hyopneumoniae combined with an oil
adjuvant.
Many studies have investigated the effect of vaccination on productivity (e.g. Vraa-
Andersen and Christensen, 1993; Charlier et al., 1994; Lium et al., 1994; Scheidt et al.,
1994; Trayer, 1994). However, several factors differed between studies, including the age
of pigs at vaccination, ef®cacy measure (e.g. ADWG and lung lesion), study periods,
housing system and group size. These variations between study designs make it dif®cult to
draw generalizable conclusions regarding the ef®cacy of any particular vaccine. Meta-
analysis is a method that takes this variability into account and increases the sample size by
combining results from several studies, thereby increasing the power to detect differences
in outcomes (Dickersin and Berlin, 1992).
Our main aim was to evaluate the effect of commercial vaccines against M. hyopneu-
moniae on the ADWG of growing pigs using a meta-analysis of published studies. Further,
the second aim was to examine the in¯uences of vaccine schedule, age of pigs, housing
system and publication quality.
1
Stellamune1 (RespiSure1 outside Europe) produced by Pfizer.
2
Suvaxyn1produced by Fort Dodge.
3
Hyoresp1 produced by Merial.
C.S. Jensen et al. / Preventive Veterinary Medicine 54 (2002) 265±278 267
Table 1
Variables provided from the individual studies evaluating the effects of vaccination against M. hyopneumoniae,
and included in the meta-analysis
We used `study' to de®ne the published study (one publication), and a `trial' to de®ne the
®eld trials conducted within a study. Some studies included more than one trial and some
studies combined results from several herds into one estimate.
Only studies using one of three commercial intramuscular vaccines (e.g. Stellamune14
(RespiSure1 outside Europe), Suvaxyn15 and Hyoresp16) were included in the meta-
analysis. From this, only studies where vaccines were randomly assigned to pigs within
herds naturally infected with M. hyopneumoniae, and with vaccinated and non-vaccinated
pigs housed in the same facilities were included for further analysis. Further information
necessary for inclusion were the sample size of vaccinated and non-vaccinated pigs, and
both the age of pigs at vaccination and whether the pigs were moved or stayed on the
original farm. Finally, the studies also had to provide ADWG, and describe the period
during which the ADWG was measured.
The vaccination schedule was classi®ed into three groups: (1) pigs vaccinated twice,
with the ®rst vaccination before weaning; (2) pigs vaccinated twice, with the ®rst
4
Stellamune1 (RespiSure1 outside Europe) produced by Pfizer.
5
Suvaxyn1produced by Fort Dodge.
6
Hyoresp1produced by Merial.
268 C.S. Jensen et al. / Preventive Veterinary Medicine 54 (2002) 265±278
vaccination at weaning; (3) pigs vaccinated at other times. Variables used in the analysis
are listed in Table 1.
Heterogeneity of the effect of vaccination among the ®eld trials on the ADWG
was tested by performing an analysis of variance including trial, vaccine status and a
2-way interaction term between trial and vaccine status (Dickersin and Berlin, 1992).
Table 2
Vaccination studies
n 39 not meeting the inclusion criteria for the meta-analysis of the effect of vaccination
against M. hyopneumoniae on the ADWG
A signi®cant interaction indicates heterogeneity. A funnel graph was made to check for
publication bias (Everitt, 1995).
With the ADWG as the outcome, an analysis of variance was performed with treatment,
age during study, vaccination schedule, housing system and publication quality as ®xed
effects. The variable describing `trial' was expressed as a random effect. The effect of
vaccination (both vaccines) on ADWG was evaluated using an orthogonal contrast
for comparison of vaccinated to non-vaccinated pigs. All variables were included in
the initial model. Backward elimination of the ®xed effects was performed to establish the
®nal model.
Table 3
Vaccination studies
n 13 included in the meta-analysis on the effect of vaccines against M. hyopneumoniae
on the ADWG
Reference Vaccine No. of ADWG ADWG Age Housing Vaccine schedule
authors type used pigsa vaccinatedb non-vaccinatedb during during (weeks after
studyc triald farrowing)
The unit of concern was the group of pigs assigned to a treatment within a trial. Trials
conducted at the same herd were treated as independent. All analyses were performed as
weighted analyses of variance using trial sample size as weights (Armitage and Berry,
1987). The assumptions for performing the analyses of ADWG were evaluated using
residual plots and test for normality. All analyses were performed using the procedure
PROC MIXED from the statistical package SAS1 (Statistical Analysis System, SAS
Institute, 1996). A signi®cance level of 5% was used.
3. Results
Sixty-three relevant publications evaluating the effect of swine respiratory vaccines were
identi®ed. Of these, three were review papers (Dayalu et al., 1992; Dayalu, 1994; Nash,
1996) and six were of trials for which the results also were published elsewhere (Vraa-
Andersen, 1994a; Vraa-Andersen et al., 1994b; Scheidt et al., 1993; Bili'c et al., 1994;
Maes et al., 1998a,b). Of the remaining 54 publications, 39 studies were not used in the
Table 4
Herd specific information
n 13 from studies included in the meta-analysis on the effect of vaccines against
M. hyopneumoniae (MH) on the ADWG
Table 5
Description of the methods, and findings on lung lesions reported for field trials included in the meta-analysis
Dalloli et al. (1998) Each lobe separately See reference See reference
Lung disease 0.70% 0.70%
Diekman et al. (1999) Mean lung score 1.30% 1.70%
Mean lung score 10.90% 5.10%
Hogg (1991) Lesion score 1.79 0.78
Le Grand and Kobisch (1996) Prevalence of pneumonia 50.00% 33.00%
Lium et al. (1994) Mean area affected 3.27% 0.85%
Mean area affected 3.27% 2.12%
Maes et al. (1998a,b) Mean area affected 17.08% 5.97%
Martinod (1996) Lung score 15.90% 4.70%
Pejsak et al. (1992) Lung score 7.90 4.40
Lung score 9.70 5.80
Lung score 12.70 6.30
Scheidt et al. (1994) Lesion score 12.00% 6.00%
Lesion score 12.00% 4.00%
Trayer (1994) Lung damage 10.41% 5.71%
Uhlenhopp (1991) Mean lesion score 23.68 16.06
Vraa-Andersen and Reported in another paperb ± ±
Christensen (1993)
Wallgren et al. (1998) Percentage of lung affected 24.60% 4.60%
Percentage of lung affected 24.60% 8.30%
a
Findings of lung lesions in non-vaccinated and vaccinated pigs.
b
Christensen and Vraa-Andersen (1993).
analysis for various reasons (Table 2). Thus, 14 studies (equaling 28 trials) met the
inclusion criteria (Table 3); 12 trials tested Stellamune1, 16 Suvaxyn1 and ®ve Hyoresp1.
Hyoresp1 was excluded from the analysis due to an insuf®cient number of trials (Kyriakis
et al., 1999 and Reynaud et al., 1998). Variance of ADWG was reported only in three
studies and therefore could not be used in our analysis (Lium et al., 1994; Wallgren et al.,
1998; Maes et al., 1999). Information on the number of herds used in ®eld trials, production
systems, herd size and information concerning respiratory diseases other than M. hyop-
neumoniae is given in Table 4. Due to missing information, these variables were not
included as covariates in the same analysis as the evaluation of lung lesions (Table 5).
Table 6
Descriptive results of the effect of Stellamune1 and Suvaxyn1 vaccines on the ADWG in the meta-analysis
(n 28 trials)
Fig. 1. Paired results on the ADWG for non-vaccinated and vaccinated pigs from the trials included in the meta-
analysis (n 28 trials).
Larger group sizes were used in ®eld trials with Stellamune1 compared to Suvaxyn1.
There was also a tendency towards a higher crude ADWG in both groups in the
Stellamune1 ®eld trials compared to Suvaxyn1 ®eld trials (Table 6).
The test of heterogeneity for ADWG among ®eld trials by vaccine status was not
signi®cant
P 0:90, indicating homogeneity among ®eld trials, and thus the results
could be pooled (Fleiss, 1986). A funnel graph further demonstrated no publication bias
(Fig. 2), and the variable `publication quality' was also non-signi®cant in the analysis.
A similar linear relationship between ADWG for vaccinated pigs compared to non-
vaccinated pigs was seen for the two vaccines (P 0:86 for identical lines) (Fig. 1).
The ®nal model for ADWG included treatment
P < 0:001 and age during the study
P < 0:001 (Table 7). The remaining variables (Table 1) were non-signi®cant.
Table 7
Results from the final model from the analysis of variance of ADWG in the meta-analysisa
4. Discussion
Many studies have shown that the vaccination of pigs against M. hyopneumoniae can
increase the ADWG in infected herds (e.g. Vraa-Andersen and Christensen, 1993; Charlier
et al., 1994; Lium et al., 1994; Scheidt et al., 1994; Wallgren et al., 1998; Maes et al., 1999).
Unfortunately, many publications fail to report whether the effect was statistically
signi®cant (e.g. Pejsak et al., 1992; Le Grand and Kobisch, 1996; Dalloli et al., 1998;
Hogg, 1991).
Meta-analysis increases the power of individual and relatively small studies by
combining results from independent studies. The increased power results in a higher
precision of the estimatesÐthereby decreasing the variance and more correctly pointing
out signi®cant results (Dickersin and Berlin, 1992).
A meta-analysis often uses the inverse variance of the outcome (effect measure) as a
weight (Fleiss, 1986). The inverse variance of the measurements in each trial is used so that
more precise trials (those with small variance) will be given a higher weight in the meta-
analysis (Armitage and Berry, 1987). However, reported ADWG variations were only
available in a few studies. As an alternative, the analysis was weighted by trial sample size.
The rationale for this is that ®eld trials with larger sample sizes tend to have a lower
variance, compared to ®eld trials with smaller sample sizes (Rosenthal, 1991).
To reduce bias, only randomized studies were included in the meta-analysis. Rando-
mization in the reported vaccine studies was mostly at the pig level (e.g. Hogg, 1991;
Dalloli et al., 1998; Maes et al., 1998c; Diekman et al., 1999), one study at litter level (Maes
et al., 1999) and one at pen level (De Jong et al., 1996). In two studies, the assignment of
pigs was based on `weeks' (e.g. pigs born in week 1 were vaccinated, pigs born in week 2
were non-vaccinated, etc.) (Dohoo and Montgomery, 1996; Pihl and Bñkbo, 1996). Some
studies did not state how the pigs were assigned, except that vaccinated and non-vaccinated
pigs were housed in the same facilities (e.g. Blagovi'c et al., 1992; Charlier et al., 1994;
Bilic et al., 1996; Karge et al., 1998). Only studies with randomization at the pig level were
included in the meta-analysis to avoid bias.
Different biases can occur when performing a meta-analysis. All available databases
were searched to avoid sampling bias. The trend towards publishing only positive
results (Rosenthal, 1979) can lead to publication bias. This is very dif®cult to assess
because it is often not possible to identify unpublished studies. A funnel graph can be
used to investigate publication bias, because publication bias will tend to skew the
pyramid shape by selectively excluding studies with small or non-signi®cant effects
(Everitt, 1995). No indication of publication bias was seen from the funnel graph (Fig. 2)
and the variable `publication quality' was non-signi®cant in the analysis of variance.
Seventy-eight percent of the studies were excluded because they did not ful®ll all of the
inclusion criteria. This might lead to exclusion bias. Most of the studies were excluded
for not reporting ®gures on the ADWG or group size, which were necessary for the
analysis.
There was a large variation between studies in the way that lung lesions were evaluated
(Table 5), and no direct standardization of the diagnostic methods was possible. For this
reason, the analyses were not based on the results of lung lesions, although this is a more
direct measure of vaccine effect. Only ®ve ®eld trials were performed with Hyoresp1
274 C.S. Jensen et al. / Preventive Veterinary Medicine 54 (2002) 265±278
Fig. 2. Funnel graph showing sample size against increase in ADWG between vaccinated and non-vaccinated
pigs for the studies included in the meta-analysis and comparing publication quality yes/no (n 28 trials).
which was excluded from the meta-analysis. This might be due to more recent marketing
(1998) of Hyoresp1 compared to the other two vaccines.
The effect of vaccination might be underestimated because only a partial vaccination of
the pig population was performed in the vaccine studies. However, in practice all pigs on a
farm are vaccinatedÐleading to greater herd immunity than in ®eld trials. In a study
estimating the cost of pneumonia (Straw et al., 1989), the ADWG decreased by 37 g for
every 10% of a pig's lungs affected by pneumonia. The results of own investigation
(Table 5) could not be directly related to those of Straw et al. (1989) due to the wide
variation among methods to characterize lung lesion among different studies.
In the present study, the average vaccination effect was a 21 g increase in ADWG
(Table 5). Because the prevalence of pneumonia in vaccination trials either differed or was
not reported, then the level of lung lesion reduction corresponding to a 21 g increase in
ADWG is unknown. The economic value of increases in ADWG might differ among herds,
but a 21 g increase might be too small to justify vaccination from an economic viewpoint.
5. Conclusion
In conclusion, the present meta-analysis of 28 published ®eld trials investigating the effect
of vaccinating pigs against M. hyopneumoniae showed that vaccinated pigs had a 21 g higher
ADWG compared to non-vaccinated pigs when adjusted for age during the study. Vaccine
type, vaccination schedule, housing system and publication quality had no signi®cant effect
on ADWG, and the funnel graph suggested that there was no publication bias.
Acknowledgements
The authors thank Dr. Margit Andreasen for discussions and comments on the manu-
script. The present study was ®nanced by Research Centre for the Management of Animal
C.S. Jensen et al. / Preventive Veterinary Medicine 54 (2002) 265±278 275
Production and Health (CEPROS), Foulum, DK-8830 Tjele, as a part of the project;
``Animal health economics. Decision support systems for disease control in pig and cattle
herds'', CEP97-5/411-231.
References
Dohoo, I.R., Montgomery, M.E., 1996. A field trial to evaluate a Mycoplasma hyopneumoniae vaccine: effects
on lung lesions and growth rates in swine. Can. Vet. J. 37, 299±302.
Everitt, B.S., 1995. The Cambridge Dictionary of Statistics in the Medical Sciences. Cambridge University
Press, Cambridge.
Fleiss, J.L., 1986. Analysis of data from multiclinical trials. Contr. Clin. Trials 7, 267±275.
Guadagnini, P.F., Alborali, L.G., Meloni, S., Martelli, P., 1998. Herd health status in finishers; lung lesions and
productive performance after Mycoplasma hyopneumoniae vaccination. In: Done, S., Thomson, J., Varley,
M. (Eds.), Proceedings of the 15th IPVS Congress, Birmingham, England, p. 156.
Harrison, R., Bryant, D., 1999. Field performance using a Mycoplasma±Atrophic rhinitis±Pasteurella±Erysipelas
combination Bacterin/toxoid: ProSystem 1B*P*M*E. AASP, pp. 207±208.
Hogg, A., 1991. Response to Mycoplasma hyopneumoniae. AASP, pp. 23±24.
Jayappa, H., Lehr, C., Tracewell, C., Wasmoen, T., 1998. Prevention of Diseases in Swine with A Mycoplasma
hyopneumoniae and Haemophilus parasuis Combination Vaccine. AASP, pp. 251±254.
Karge, I., SchroÈder, L., Elsen, R., 1998. Vaccination of young piglets against Mycoplasma hyopneumoniaeÐ
evaluation of economic parameters. In: Done, S., Thomson, J., Varley, M. (Eds.), Proceedings of the 15th
IPVS Congress, Birmingham, England, p. 148.
Kobisch, M., LabbeÂ, A., Morvan, P., Carolet, R., 1994. Evaluation of a Mycoplasma hyopneumonia vaccine in
pigs experimentally infected with Mycoplasma hyopneumoniae and Pasteurella multocida. In: Poomvises, P.,
Ingkaninun, P. (Eds.), Proceedings of the 13th IPVS Congress, Bangkok, Thailand, p. 194.
Kyriakis, S.C., Alexopoulos, C., Viemmas, J., Sarris, K., Lekkas, S., Koutsoviti-Papadopoulous, M., Saoulidis,
K., 1999. Field experience on performance improvement after vaccination with HYORESP in Mycoplasma
hyopneumoniae infected commercial pig unit. Eur. Focus, 21.
Le Grand, A., Kobisch, M., 1996. Enzootic pneumonia: comparison of the effect of pulse medication and
vaccination. In: Proceedings of the 14th IPVS Congress, Bologna, Italy, p. 223.
Lium, B., Lund, A., Skomsùy, A., 1994. A field study on vaccination against Mycoplasma hyopneumoniae
infection in pigs. In: Poomvises, P., Ingkaninun, P. (Eds.), Proceedings of the 13th IPVS Congress, Bangkok,
Thailand, p. 191.
Maes, D., Verdonck, M., Castryck, F., Vrijens, B., Verebek, W., Viaene, J., de Kruif, A., 1998a. The effect of
vaccination against Mycoplasma hyopneumoniae in pig herds with an all-in/all-out production system. In:
Done, S., Thomson, J., Varley, M. (Eds.), Proceedings of the 15th IPVS Congress, Birmingham, England, p. 152.
Maes, D., Verdonck, M., Castryck, F., Miry, C., Gielis, D., Vrijens, B., de Kruif, A., 1998b. The effect of
vaccination against Mycoplasma hyopneumoniae in pig herds with a continuous production system. In:
Done, S., Thomson, J., Varley, M. (Eds.), 15th IPVS Congress, Birmingham, England, p. 153.
Maes, D., Deluyker, H., Verdonck, M., Castryck, F., Miry, C., Lein, A., Vrijens, B., De Kruif, A., 1998c. The
effect of vaccination against Mycoplasma hyopneumoniae in pig herds with a continuous production system.
J. Vet. Med. Ser. B 45, 495±505.
Maes, D., Deluyker, D., Verdonck, M., Castryck, F., Miry, C., Vrijens, B., Verebek, W., Viaene, J., de Kruif, A.,
1999. Affect of vaccination against Mycoplasma hyopneumoniae in pig herds with all-in/all-out production
system. Vaccine 17, 1024±1034.
Martinod, S., 1996. Protection against Mycoplasma hyopneumoniae and Actinobacillus pleuropneumoniae
infections using a mycoplasma inactive vaccine RespiSure under field conditions. In: Proceedings of the 14th
IPVS Congress, Bologna, Italy, p. 221.
Martinon, O., Tiberghien, M.P., Reynaud, G., Blanchet, M., Brun, A., Milward, F., 1998a. Efficacy of
Mycoplasma hyopneumoniae Bacterin (Hyoresp) in challenge studies. In: Done, S., Thomson, J., Varley, M.
(Eds.), Proceedings of the 15th IPVS Congress, Birmingham, England, p. 157.
Martinon, O., Tiberghien, M.P., Reynaud, G., Blanchet, M., Brun, A., Milward, F., 1998b. Efficacy of a `on shot'
schedule of Mycoplasma hyopneumoniae Bacterin (Hyoresp). In: Done, S., Thomson, J., Varley, M. (Eds.),
Proceedings of the 15th IPVS Congress, Birmingham, England, p. 284.
Martinon, O., Tiberghien, M.P., Reynaud, G., Blanchet, M., Brun, A., Milward, F., 1998c. Duration of immunity
of a Mycoplasma hyopneumoniae Bacterin (Hyoresp). In: Done, S., Thomson, J., Varley, M. (Eds.),
Proceedings of the 15th IPVS, Birmingham, England, p. 285.
Miller, S.K., Ross, R.F., Erickson, B.Z., Gerber, D., Schultz, R.H., Chladek, D.W., 1992. Response of pigs
vaccinated with Mycoplasma hyopneumoniae vaccines to challenge with virulent Mycoplasma hyopneu-
moniae. In: Proceedings of the IPVS Congress, Hague, The Netherlands, p. 324.
C.S. Jensen et al. / Preventive Veterinary Medicine 54 (2002) 265±278 277
Moore, C., Daigneault, J., Hoover, T.C., 1997. Efficacy of Different Strategies of Mycoplasma Vaccination As
Measured by Serology. AASP, pp. 135±136.
Morrow, W.E.M., Iglesias, G., Stanislaw, C., Stepphenson, A., Erickson, G., 1994. Effect of a mycoplasma
vaccine on average daily gain in swine. Swine Health Prod. 2 (6), 13±18.
MunÄoz, A., PallareÂs, F.J., Ramis, G., 1996a. Study of the effect of vaccination with Stellamune mycoplasma1 on
enzootic pneumoniaÐrelated clinical and productive parameters under field conditions. In: Proceedings of
the 14th IPVS Congress, Bologna, Italy, p. 229.
MunÄoz, A., PallareÂs, F.J., Ramis, G., 1996b. Use of a general linear model to evaluate the effect of vaccination of
swine with Stellamune mycoplasma1 on zootechnical performance and financial gain. In: Proceedings of the
14th IPVS Congress, Bologna, Italy, p. 222.
Murphy, D.A., van Alstine, W.G., Clark, L.K., Albregts, S., Knox, K., 1993. Aerosol vaccination of pigs against
Mycoplasma hyopneumoniae infection. Am. J. Vet. Res. 54 (11), 1874±1880.
Nash, W.A., 1996. Mycoplasma hyopneumoniae vaccination and disease control. Pig. J. 37, 78±94.
Okada, M., Okonogi, H., Ono, M., Sakano, T., Sato, S., 1998. Evaluation of Mycoplasma hyopneumoniae
vaccine in pigs under experimental and field condition. In: Done, S., Thomson, J., Varley, M. (Eds.),
Proceedings of the 15th IPVS Congress, Birmingham, England, p. 290.
Pejsak, Z., Tarasiuk, K., Cazin, P., 1992. Vaccination against mycoplasmal pneumoniaÐa field study on
RespiSure. In: Proceedings of the 12th IPVS, Hague, The Netherlands, p. 325.
Petersen, G.R., Weiss, D., 1992. Vaccination against mycoplasma hyopneumoniae in swine. Pig. Vet. J. 28,
35±39.
Petersen, G., Weiss, D., Egan, J., Korshus, J., Peters, R., Miron, M., 1991. Response to Mycoplasma
hyopneumoniaeÐvaccination in nursering piglets. AASP, pp. 17±21.
Pihl, K., Bñkbo, P., 1996. Vaccination mod mycoplasma-lungesyge hos svin. Vet. Inform. 6, 3±5.
Reynaud, G., Brun, A., Milward, F., Lacoste, F., Vandeputte, J., 1992. Clinical results obtained with an
inactivated vaccine against porcine mycoplasmosis. In: Proceedings of the 12th IPVS Congress, Hague, The
Netherlands, p. 303.
Reynaud, G., Martinon, O., Chouvet, C., Brun, A., Milward, F., 1998. Clinical field trial with Mycoplasma
hyopneumoniae bacterin (hyoresp). In: Done, S., Thomson, J., Varley, M. (Eds.), Proceedings of the 15th
IPVS Congress, Birmingham, England, p. 150.
Rosenthal, R., 1979. The ``fiel drawer problem'' and tolerance for null results. Psychol. Bull. 86 (3), 638±641.
Rosenthal, R., 1991. Meta-analytic Procedures for Social Research. Saga Publication.
Ross, R.F., 1999. Mycoplasmal diseases. In. Straw, B.E., D'Allaire, S., Menegeling, W.L., Taylor, D.J. (Eds.),
Proceedings of the Eighth Diseases of Swine. Iowa State University Press, Ames, IA, pp. 495±510.
SAS Institute, 1996. SAS/STAT Software, Changes and Enhancement, Version 6.11. SAS Institute, Inc., Cary,
NC, 1996. ISBN 1555442749.
Scheidt, A.B., Mayrose, V.B., Van Alstine, W.G., Clark, L.K., Cline, T.R., Einstein, M.E., 1993. The Benefit to
Cost Ratio of Vaccinating Pigs for Mycoplasmal Pneumonia in a Swine herd Affected by Enzootic
Pneumonia. AASP, pp. 29±30.
Scheidt, A.B., Mayrose, V.B., Van Alstine, W.G., Clark, L.K., Cline, T.R., Einstein, M.E., 1994. The effects of
vaccinating pigs for mycoplasmal pneumonia in a swine herd affected by enzootic pneumonia. Swine Health
Prod. 2 (1), 7±11.
Sheldrake, R.F., Gardener, I.A., Saunders, M.M., Romalis, L.F., 1991. Intraperitonal vaccination of pigs to
control Mycoplasma hyopneumoniae. RVTSA 51, 285±291.
Sheldrake, R.F., Romalis, L.F., Saunders, M.M., 1993. Serum and mucosal antibody responses against
Mycoplasma hyopneumoniae following intraperitonal vaccination and challenge of pigs with M
hyopneumoniae. RVTSA 55, 371±376.
Straw, B.E., Tuovinen, V.K., Bigras-Poulin, M., 1989. Estimation of the cost of pneumonia in swine herds.
JAVMA 12, 1702±1706.
Stripkovits, L., Miller, D.J.S., 1993. Comparative Studies of the Efficacy of Mycoplasma Hyopneumonia
Vaccine (RespiSure), Lincomycin and Tiamulin Against Experimental M. hyopneumoniae Infection of
Piglets. AASP, pp. 17±26.
Thacker, B., Boettcher, T., Anderson, T., Thacker, E., Young, T., 1998a. The influence of passive immunity on
serological responses to Mycoplasma hyopneumoniae vaccine. In: Done, S., Thomson, J., Varley, M. (Eds.),
Proceedings of the 15th IPVS Congress, Birmingham, England, p. 154.
278 C.S. Jensen et al. / Preventive Veterinary Medicine 54 (2002) 265±278
Thacker, E.L., Thacker, B.J., Boettcher, T.B., Jayappa, H., 1998b. Comparison of antibody production,
lymphocyte stimulation, and protection induced by four commercial Mycoplasma hyopneumoniae bacterins.
Swine Health Prod. 6 (3), 107±112.
Thacker, E.L., Thacker, B.J., Jayappa, H., 1998c. Evaluation of humeral and cellular immune response and
protection induced in pigs by five commercial mycoplasma vaccines. In: Done, S., Thomson, J., Varley, M.
(Eds.), Proceedings of the 15th IPVS Congress, Birmingham, England, p. 151.
Thacker, E.L., Halbur, P.G., Thacker, B.J., 1999. Effect of Vaccination on Dual Infection with Mycoplasma
hyopneumoniae and PRRV. AASP, pp. 375±377.
Trayer, T., 1994. Performance of Pigs Vaccinated with RespiSure in All-in/All-out Housing. AASP, pp. 23±25.
Uhlenhopp, E.K., 1991. Suvaxyn Respired MH: Findings From the Field. AASP, pp. 123±131.
Vraa-Andersen, L., 1994a. Respiratory diseases in Danish slaughter swine application of epidemiological
methods. Ph.D. Thesis. KVL, Denmark.
Vraa-Andersen, L., Christensen, G., 1993. Forebyggelse af almindelig lungesyge. Dan Dyrlaegeforen Medlemsb
76 (4), 129±132.
Vraa-Andersen, L., Christensen, G., Kuiper, R., 1994b. Vaccine efficiency trial with Suvaxyn M. hyo in
Denmark. In: Poomvises, P., Ingkaninun, P. (Eds.), Proceedings of the 13th IPVS, Bangkok, Thailand, p. 192.
Wallgren, P., LoÈfstedt, M., Heldmer, E., 1998. Strategic vaccination against Mycoplasma hyopneumoniae to
avoid marketing contagious animals from multiplying herds. In: Done, S., Thomson, J., Varley, M. (Eds.),
Proceedings of the 15th IPVS Congress, Birmingham, England, p. 149.
Weiss, D.L., Peterson, G.R., 1992. Mycoplasma hyopneumoniae Bacterin field efficacy study. In: Proceedings of
the 12th IPVS Congress, Hague, The Netherlands, p. 305.
Weng, C.N., Tzan, Y.L., Liu, S.D., Lin, S.Y., Lee, C.J., 1992. Protective effects of an oral microencapsulated
Mycoplasma hyopneumoniae vaccine against experimental infected pigs. RVTSA 53, 42±46.