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SRBESSENTIALS
05
Effect of vaccination against bovine herpesvirus 1 with
inactivated gE-negative marker vaccines on the health of
dairy cattle herds.
Kerli Raaperi*, Toomas Orro, Arvo Viltrop
Institute of Veterinary Medicine and Animal Sciences, Estonian University of Life Sciences, Kreutzwaldi 62, Tartu 51014, Estonia
THE PLACE FOR
THE EXPERTS IN
CATTLE DISEASES
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Contents lists available at ScienceDirect
Preventive Veterinary Medicine
journal homepage: www.elsevier.com/locate/prevetmed
Effect of vaccination against bovine herpesvirus 1 with
inactivated gE-negative marker vaccines on the health of
dairy cattle herds
Kerli Raaperi ∗ , Toomas Orro, Arvo Viltrop
Institute of Veterinary Medicine and Animal Sciences, Estonian University of Life Sciences, Kreutzwaldi 62, Tartu 51014, Estonia
a r t i c l e
i n f o
Article history:
Received 23 March 2014
Received in revised form 13 January 2015
Accepted 17 January 2015
Keywords:
Bovine herpesvirus 1
Vaccination
Herd health
Reproduction
Respiratory disease
a b s t r a c t
The aim of this study was to estimate the effect of the bovine herpesvirus 1 (BHV-1) vaccination on herd health and production in BHV-1 infected Estonian dairy cattle herds. Seven
herds vaccinated with inactivated gE-negative BHV-1 marker vaccines and seven matched
non-vaccinated herds were selected. In vaccinated herds the calving interval was on average 7.01 days shorter compared to that in the non-vaccinated herds (coef = −7.01, 95%
CI = −11.98, −2.03, p = 0.008) during the study period (2007–2012). In non-vaccinated herds
the insemination index had an increasing trend (coef(log scale) = 0.03, 95% CI = −0.003,
0.06, p = 0.054) and the first service conception rate decreased (coef = −2.19, 95% CI = −3.91,
−0.47, p = 0.015), whereas no significant changes occurred in vaccinated herds. Average
yearly milk yield per cow increased (coef = 145.30, 95% CI = −6.11, 296.71, p = 0.065) and
length of the dry period decreased in BHV-1 vaccinated herds (coef(log scale) = −0.02,
95% CI = −0.04, 0.004, p = 0.056) compared to non-vaccinated herds during the study years.
Youngstock and the cow culling rate due to respiratory disease was significantly lower in
vaccinated herds compared to non-vaccinated herds (coef = −0.29, 95% CI = −0.47, −0.11,
p = 0.003 and coef = −0.15, 95% CI = −0.29, −0.007, p = 0.043, respectively). These results
suggest that vaccination against BHV-1 is associated with herd health and productivity.
© 2015 Elsevier B.V. All rights reserved.
1. Introduction
Bovine herpesvirus 1 (BHV-1) is an important cattle pathogen causing infectious bovine rhinotracheitis
(IBR), infectious pustulous vulvovaginitis/balanoposthitis
(IPV/IPB), abortions as well as systemic illness in young
calves. BHV-1 establishes life-long latency following acute
infection and can reactivate under unfavourable conditions
for the virus-carrier animal (Kaashoek et al., 1996; Jones
and Chowdhury, 2007).
∗ Corresponding author. Tel.: +372 56219397; fax: +372 7313706.
E-mail address: [email protected] (K. Raaperi).
Several countries and larger districts of a few countries
are to date recognised as IBR-free. European Commissionapproved eradication programmes are ongoing in some
countries and regions to which the additional guarantees
for IBR apply (2011/674/EU). In addition to negative influences on animal health, IBR has become a limiting factor in
livestock trade (64/432/EEC Article 9).
Eradication programmes relying entirely or partly on
BHV-1 DIVA vaccines (syn. marker vaccines) are currently
running in several countries. A DIVA vaccine carries at
least one antigenic protein less than the corresponding
wild-type virus. After infection, but not after vaccination, it is possible to detect an antibody response for the
specific protein with a companion diagnostic test (van
Oirschot, 1999). To date, only glycoprotein E-deleted virus
http://dx.doi.org/10.1016/j.prevetmed.2015.01.014
0167-5877/© 2015 Elsevier B.V. All rights reserved.
Please cite this article in press as: Raaperi, K., et al., Effect of vaccination against bovine herpesvirus
1 with inactivated gE-negative marker vaccines on the health of dairy cattle herds. PREVET (2015),
http://dx.doi.org/10.1016/j.prevetmed.2015.01.014
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2
vaccines are in use in the European Union for IBR eradication (Sanco/C3/AH/R20/2000). Continuous vaccination
with live or inactivated gE-negative vaccines is reducing
the circulation of the virus within a herd (Bosch et al., 1998;
Mars et al., 2001; Makoschey et al., 2007; Vilmos et al.,
2007; Jacevičius et al., 2008; Ampe et al., 2012; Raaperi
et al., 2012a). By limiting the risk of having new BHV-1
gE-positive animals within the herd and by the gradual
culling of field virus-infected animals, the herd may achieve
IBR-free status (Makoschey and Bielsa, 2007).
Published reports on the impact of BHV-1 infections and
outbreaks of BHV-1 on animal health under field conditions have described reduced milk production, an increase
of respiratory disease, higher mortality of calves as well
as reproductive problems (Allan et al., 1980; Janzen et al.,
1980; Wiseman et al., 1980; Greig et al., 1981; Cook, 1998;
van Schaik et al., 1999; Holzhauer et al., 2003; Rissi et al.,
2008). On the other hand, subclinical spread of BHV-1 in
a naive herd has been demonstrated (van Oirschot et al.,
1993; Hage et al., 1998; Pritchard et al., 2003). Clinical and
pathological effects of BHV-1 infection have been shown in
experimental challenge studies (Bitsch, 1973; Miller and
Van der Maaten, 1987; Belknap et al., 1994). Several studies showed associations between the prevalence of BHV-1
serum antibodies and impaired health and performance
in cattle herds (Biuk-Rudan et al., 1999; Waldner, 2005;
Mineo et al., 2006; Raaperi et al., 2012b,c; Roshtkhari et al.,
2012). Most of the experimental and observational studies have followed an epidemic of IBR in a previously naive
herd in order to estimate losses. In countries where BHV-1
infection is endemic, a number of herds are permanently
infected and clinical manifestations of the BHV-1 infection
may not be as obvious as that following the first introduction of the virus. Due to overlapping clinical manifestation
of several infections causing respiratory and reproductive disorders, contribution of the IBR virus to the overall
performance of the animals within the herd is obscure.
Concerning BHV-1, implementation of a vaccination protocol may reduce or eliminate the impact of the infection
on herd health. Comparing vaccinated herds with those
not implementing any control measures against BHV-1,
enables evaluating the actual role of IBR infection in herd
health in real farm conditions. Asking the farmer’s opinion about the change in herd health during vaccinating
years would allow evaluation of whether the changes are
recognisable to the farmer.
The objective of this study was to estimate the impact of
BHV-1 infection on health and performance of dairy cattle
herds via the evaluation of the effect of vaccination with
inactivated gE-negative marker vaccines.
2. Materials and methods
2.1. Study design
2.1.1. Herd selection
After the prevalence study of Raaperi et al. (2010), control programmes were composed for seven dairy cattle
herds aiming to eradicate the virus from the herds. Characteristics of those herds are given in Table 1 (V+ herds). In
those herds, inactivated gE-negative marker vaccines were
used for all animals over three months of age twice a year.
Rispoval IBR Marker inactivatum (Pfizer Animal Health) (V+
I, II, III, IV, V and VII) and/or Bovilis IBR marker inac. (Intervet International) (V+ V and VI) were used (Raaperi et al.,
2012a). Herds started with the vaccination between April
2007 and November 2008.
Also, seven non-vaccinated dairy herds were selected
and matched individually with vaccinated herds based on
the information available from BHV-1 prevalence study
conducted from 2006 to 2008 (Raaperi et al., 2010). Matching criteria were: similar herd size, milk productivity,
breed, animal keeping system, BHV-1 prevalence before
vaccination and herd bovine viral diarrhoea virus (BVDV)
status. None of the participating herds had vaccinated
against BHV-1 or BVDV before (Raaperi et al., 2010).
Description of the herds included in this study is given in
Table 1.
2.1.2. Data collection
Herd health data for the years 2007–2012 were received
from the Estonian Animal Recording Centre (EARC). For the
two herds that started IBR vaccination in 2008, data of five
years (2008–2012) were included and consequently also
for the two non-vaccinated herds. In five herds the vaccination programme was initiated in 2007 and therefore
six study years (2007–2012) were included for those herds
as well as for the five non-vaccinated herds. The dataset
contained 80 records in total. An internet questionnaire
was composed for all vaccinating farms and completed by
the farmer or farm manager. A pre-testing of the questionnaire was accomplished by sending the questionnaire to
one farmer not participating in the study. After completion
the author had a discussion with the test farmer to discover
if any of the questions were confusing. All the comments
of the test farmer were taken into account to improve the
questionnaire.
The questionnaire was composed to collect information
about the continuation and regularity of the vaccination
programme in order to confirm the suitability of the herd
to be included. Specific questions were asked about the
change in respiratory disease incidence in calves, heifers
and cows, calf mortality, abortion incidence in heifers
and cows, reproduction performance of heifers and cows,
and milk production and treatment costs (antimicrobial
drugs) compared to the pre-vaccination period. For that,
multiple-choice questions with pre-defined answer categories (‘increased’, ‘decreased’, ‘remained the same’, ‘don’t
know’) were used.
We also questioned farmers from non-vaccinating
farms about vaccinations against BHV-1 in the last ten years
in order to confirm the suitability of the farm as a ‘nonvaccinated herd’ in our study.
2.1.3. Data analysis
Linear mixed-effects models were constructed to
evaluate the effect of vaccination to herd health and
productivity parameters. Outcome variables analysed
were ‘calving interval’, ‘average cow milk production’,
‘average somatic cell count’, ‘first service conception rate’,
‘insemination index’ (number of inseminations per pregnancy), ‘herd average number of lactations’, ‘days from
Please cite this article in press as: Raaperi, K., et al., Effect of vaccination against bovine herpesvirus
1 with inactivated gE-negative marker vaccines on the health of dairy cattle herds. PREVET (2015),
http://dx.doi.org/10.1016/j.prevetmed.2015.01.014
V− I
V+ II
V− II
V+ III
V− III
V+ IV
V− IV
V+ V
V− V
V+ VI
V− VI
V+ VII
V− VII
402
7523
EH, ER
415
6200
EH, ER
1000
8369
EH, ER
1000
7238
EH
530
7000
EH, ER
613
7400
EH, ER
1820
8416
EH
524
8700
EH, ER
2187
8325
EH
832
6301
EH, ER
674
8300
EH
1791
6400
EH
619
8085
EH, ER
608
8284
EH
Farm management
Number of barns
Veterinarian is the employee of
the farm
Inseminator is the employee of
the farm
Using bull
1
Yes
>1
Yes
>1
Yes
>1
Yes
>1
Yes
>1
No
>1
Yes
>1
Yes
>1
Yes
>1
No
>1
Yes
>1
Yes
>1
No
>1
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
No
No
No
H
C
H
H
H
No
H
No
H
No
No
No
No
No
No
No
No
Yes
Yes
Yes
No
Yes
Yes
Yes
Yes
≥2
≥2
≥2
≥2
≥2
≥2
0
≥2
≥2
≥2
≥2
1
≥2
0
Farm biosecurity
Inseminator gives service to
other farms
Number of animals purchased
in last 3 years
Cow management
Barn type
Keeping system
Grazing
CB
L
Yes
CB
L
No
CB
L
No
CB
L
Yes
CB
L
No
CB
L
Yes
CB
L
No
CB
L
No
CB
L
No
CB
L
Yes
WB
F
Yes
WB
F
Yes
WB
F
Yes
WB
F
Yes
Youngstock
management
Way of keeping
Keeping system
Relocating animals between
the barns (number of times per
year)
Grazing
TC
M
0
S
L
>2
S
M
>2
S
M
>2
S
M
2
S
L
>2
S
M
>2
S
L
>2
S
M
>2
S
L
>2
S
L
>2
S
M
>2
S
F
>2
S
M
>2
Yes
No
No
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Infection status
Herd BVD status
IBR prevalence in cows
IBR prevalence in youngstock
Pos
90
38
Neg
81
4
Pos
84
24
Neg
51
9
Pos
89
91
Pos
95
63
Pos
95
89
Neg
100
16
Pos
97
60
Neg
21
7
Pos
98
44
Pos
92
89
Pos
67
2
Neg
48
0
V+ – vaccinated, V− – non-vaccinated, EH – Estonian Holstein, ER – Estonian Red, H – heifers, C – cows, CB – cold barn, WB – warm barn, F – fixed, L – loose, M – mixed, TC – together with cows, S – separately
from cows, Pos – positive, Neg – negative.
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Number of cows
Year milk production (kg/cow)
Breed
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Farm
Farm characteristics
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Please cite this article in press as: Raaperi, K., et al., Effect of vaccination against bovine herpesvirus
1 with inactivated gE-negative marker vaccines on the health of dairy cattle herds. PREVET (2015),
http://dx.doi.org/10.1016/j.prevetmed.2015.01.014
Table 1
Description of herds in the longitudinal bovine herpesvirus 1 vaccination study during 2007–2012 in Estonia.
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calving to first pregnancy’, ‘age of first calving’, ‘length of
dry period’, ‘youngstock (from first days of life to calving)
culling rate (number of youngstock culled/total number
of cows in 31st December*100)’, ‘youngstock culling
rate due to: respiratory disease/reproduction problems/
abortions/appearance fault/selling/digestive disorders/
metabolic disorders/foot disorders/infectious diseases/
traumas/loosing/accident/meat
production/fattening/
other reasons’ (number of youngstock culled due to given
reason/total number of cows*100), ‘cow culling rate’
(number of cows culled/total number of cows*100), ‘cow
culling rate due to: age/low productivity/udder diseases
and mastitis/reproduction problems/abortion/difficult
calving/foot disorders/digestive disorders/respiratory diseases/infectious diseases/traumas/loosing/accident/other
reasons (number of cows culled due to given reason/total number of cows*100)’, ‘abortion % (number
of abortions/total number of cows*100)’ and ‘stillbirth
% (number of stillbirths/total number of cows*100)’.
Fixed effects for the model were ‘year’ and ‘vaccination
status’ (vaccinated/non-vaccinated) with interaction term
between those two. The herd itself was considered a
random effect. As our main interest was to determine the
trend over time of the outcome variable with our models,
‘year’ was included as a continuous variable.
General equation of the linear mixed models was as
follows:
Yi = ˇ0 + ˇ1 X1(i) ∗ X2(i) + uherd(i) + εi
in which Y is the outcome variable, ˇ0 is the intercept, ˇ1 is
the size of the effect of independent variables X1 (year) and
X2 (herd category: vaccinated or not-vaccinated), uherd(i) is
the random effect (herd) with the first-order autoregressive (AR1) covariance structure for repeated measures and
εi is an error term.
Linearity of the relationship was controlled graphically
and statistically. In order to check if the relationship was
curvilinear, square, cubic and quadratic terms for ‘year’
were inspected for significance. In order to confirm constant variance and residual normality, a residual plot of the
model was composed to detect for homoscedasticity and
q–q plots to check residuals for normality. Residuals were
plotted against independent variables to discover hidden
patterns. Significance of the random effect was evaluated
by comparing models using likelihood ratio test (Table 2).
Four models showed positive log likelihood values, however the model with a random effect gave AIC and BIC
values closer to negative infinity and was therefore considered better in terms of statistical fitness. In order to
complete the linearity assumption of the linear models, values of the variables ‘insemination index’ and ‘length of dry
period’ were log-transformed and square root was taken
from ‘youngstock culling rate’.
R version 2.13.0 (The R Foundation for Statistical Computing) was used for linear mixed model building via using
the lme function. The variables ‘youngstock culling rate
due to respiratory disease’ and ‘cow culling rate due to
respiratory disease’ had a negative binomial distribution;
therefore mixed-effects negative binomial models were
composed for those parameters. Statistical software SAS
version 9.2 (SAS Institute Inc., USA) with GLIMMIX procedure was used for these models.
Descriptive statistics were used to summarise the
responses to questionnaires.
3. Results
3.1. Effect of BHV-1 vaccination on health and
productivity of dairy cattle
Results of the outcome variables significantly associated with vaccination status are presented in Table 2.
Figs. 1 and 2 present the raw data together with results
of the statistical models in which the significance of the
main effect year (Y) in vaccinated (V+) and non-vaccinated
herds (V−) as well as the interaction between the year and
vaccination status of the farm (Y*V) is presented. The trend
of change in the two groups of herds is given with lines of
average fitted values obtained from the model. For graphical presentation the model results were back-transformed
to the original scale (Figs. 1 and 2). In V+ herds the calving interval showed a decreasing trend over six years
(coef = −7.01 days, 95% CI = −11.98, −2.03, p = 0.008) compared to the non-vaccinated herds. The insemination index
demonstrated an increasing trend (coef(log scale) = 0.03,
95% CI = −0.003, 0.06, p = 0.054) and the first service conception rate decreased (coef = −2.19, 95% CI = −3.91, −0.47,
p = 0.015) in V− herds, whereas insignificant change was
ascertained in vaccinated herds during study years (Fig. 1,
Table 2).
Average yearly milk yield per cow increased
(coef = 145.30 kg, 95% CI = −6.11, 296.71, p = 0.065) and
length of the dry period decreased (coef(log scale) = −0.02,
95% CI = −0.04, 0.004, p = 0.056) in V+ herds compared to
non-vaccinated herds (Fig. 1, Table 2).
The youngstock culling rate was higher in V+ herds
(coef(square root) = 0.20, 95% CI = −0.002, 0.40, p = 0.054)
compared to V− herds. The youngstock culling rate due
to respiratory disease increased in V− herds (coef = 0.24,
95% CI = 0.12, 0.36, p < 0.001), whereas no statistically significant change was ascertained in V+ herds (p = 0.461).
The same trend was observed among cows where culling
rate due to respiratory disease was lower in V+ herds
(coef = −0.15, 95% CI = −0.29, −0.007, p = 0.043) than in V−
herds (Fig. 2, Table 2).
3.2. Results of questionnaire data
Six out of seven vaccinating farmers completed the
internet questionnaire. Five farmers declared that they
have been vaccinating continuously and no vaccination
round was skipped. ‘V+ V’ farm stated that due to financial problems vaccination was halted from spring 2012
to spring 2013. All farmers of the non-vaccinated herds
confirmed that they had not been vaccinating against
BHV-1.
According to the farmers’ opinions, calf respiratory disease incidence decreased in five out of six vaccinating
farms and increased in one herd (V+ II) compared to the
pre-vaccination period. Farmers claimed that after starting with vaccination, respiratory disease incidence among
Please cite this article in press as: Raaperi, K., et al., Effect of vaccination against bovine herpesvirus
1 with inactivated gE-negative marker vaccines on the health of dairy cattle herds. PREVET (2015),
http://dx.doi.org/10.1016/j.prevetmed.2015.01.014
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Table 2
Results of the linear and negative binomial mixed-effect models for longitudinal bovine herpesvirus 1 vaccination study during 2007–2012 in Estonia.
p-Value
95% CI
Random effect p-value
LogLik (MM)
LogLik (FEM)
Calving interval (days)
410.15
Intercept
3.44
Y
23.44
V+
Y*V+
−7.01
Coefficient
0.000
0.06
0.071
0.008
393.73; 426.57
−0.08; 6.96
0.22; 46.66
−11.98; −2.03
<0.0001
−325.06
−342.18
Milk production (kg/year)
8148.17
Intercept
65.39
Y
−561.29
V+
145.30
Y*V+
0.000
0.236
0.289
0.065
7446.62; 8849.72
−41.68; 172.46
−1553.43; 430.85
−6.11; 296.71
<0.0001
−589.41
−628.86
Insemination index (log scale)
0.61
Intercept
0.03
Y
V+
0.30
−0.05
Y*V+
0.000
0.054
0.047
0.033
0.42; 0.80
−0.003; 0.06
0.04; 0.56
−0.10; −0.003
<0.0001
44.21
1.72
Length of dry period (days) (log scale)
4.25
0.000
Intercept
−0.004
0.643
Y
0.05
0.407
V+
Y*V+
−0.02
0.056
4.17; 4.33
−0.02; 0.01
−0.06; 0.16
−0.04; 0.004
<0.0001
70.91
57.20
First service conception rate (%)
53.18
Intercept
Y
−2.19
−16.44
V+
3.14
Y*V+
43.08; 63.28
−3.91; −0.47
−30.73; −2.15
0.71; 5.57
<0.0001
−262.88
−303.56
2.98; 4.26
−0.19; 0.09
−2.00; −0.18
−0.002; 0.40
<0.0001
−74.16
−92.59
<0.0001
206.87
253.32
<0.0001
167.73
137.61
0.000
0.015
0.044
0.014
Youngstock culling rate (%) (square root)
Intercept
3.62
0.000
−0.05
0.535
Y
−1.09
0.036
V+
Y*V+
0.20
0.054
Youngstock culling rate (%) due to respiratory diseasea
Intercept
−0.51
0.204
−1.29; 0.26
0.24
0.0004
0.12; 0.36
Y
0.86
0.128
−0.21; 1.93
V+
Y*V+
−0.29
0.003
−0.47; −0.11
Cow culling rate (%) due to respiratory diseasea
Intercept
−0.74
0.122
0.11
0.054
Y
V+
0.03
0.969
−0.15
0.043
Y*V+
−1.62; 0.15
0.0001; 0.21
−1.20; 1.25
−0.29; −0.007
a
Negative binomial mixed-effects model.
MM – mixed effect model, FEM – fixed effect model, Y – year, V – vaccination status, V+ – vaccinated herds.
heifers and cows has decreased in six and four herds out of
six, respectively. Farmers indicated that calf mortality also
decreased in five out of six herds (V+ I, II, III, V, VII) during
the vaccination period. Heifer and cow abortion incidence
was ascertained to decrease in one (V+ II) and two herds (V+
III and IV) respectively, whereas increase in abortion incidence was not indicated by any of the vaccinating farms.
Two farmers (V+ II and III) stated that overall reproduction status improved after starting IBR vaccination, three
of them (V+ I, V, VII) stated that it remained the same and
one (V+ IV) could not answer the question. Milk productivity was estimated to increase in three farms (V+ II, III, VII)
out of six and treatment costs were stated to be increased
in two farms (V+ II, III) and decreased in two vaccinated
herds (V+ I, IV) (Table 3).
An open question asked to specify any other change
occurring during the vaccination period that was not asked
in the questionnaire. The farmer from herd ‘V+ IV’ reported
that in addition to reduced incidence of pneumonia, there
was a decrease in conjunctivitis cases and therefore less
blindness in animals.
4. Discussion
The aim of this study was to estimate the impact of
BHV-1 infection on health and performance of dairy cattle
herds via the evaluation of the effect of vaccination with
inactivated gE-negative marker vaccines.
4.1. Change in herd health related to vaccination against
BHV-1
4.1.1. Respiratory disease
Most of the farmers claimed they experienced a decline
in calf, heifer and cow respiratory disease as well as calf
mortality in the vaccination period compared with the
Please cite this article in press as: Raaperi, K., et al., Effect of vaccination against bovine herpesvirus
1 with inactivated gE-negative marker vaccines on the health of dairy cattle herds. PREVET (2015),
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A
Calving inte rval (days)
500
V+
V-
Y(V-)
Y(V+)
Y*V
475
p = 0.060
p = 0.051
p = 0.008
450
425
400
375
2007
2008
2009
2010
2011
2012
Year
Average cow milk production (kg/year)
K. Raaperi et al. / Preventive Veterinary Medicine xxx (2015) xxx–xxx
6
V+
V-
4.0
Y(V-)
Y(V+)
Y*V
p = 0.054
p = 0.269
p = 0.033
Length of dry pe riod (days)
Insemination index
Y(V-)
Y(V+)
Y*V
V+
V-
11000
p = 0.236
p < 0.001
p = 0.065
10000
9000
8000
7000
6000
2007
2008
2009
2010
2011
2012
Ye ar
D
C
4.5
3.5
3.0
2.5
2.0
1.5
2007
2008
2009
2010
2011
2012
Year
First service conception rate (%)
B
12000
100
V+
Y(V-)
Y(V+)
Y*V
V-
90
p = 0.643
p = 0.002
p = 0.056
80
70
60
50
2007
2008
2009
2010
2011
2012
Ye ar
E
90
Y(V-)
Y(V+)
Y*V
V+
V-
80
p = 0.015
p = 0.285
p = 0.014
70
60
50
40
30
20
2007
2008
2009
2010
2011
2012
Ye ar
Fig. 1. Reproduction and productivity parameters in herds of a longitudinal bovine herpesvirus 1 vaccination study during years 2007–2012 in Estonia.
Graph points represent the raw data in vaccinated () and non-vaccinated herds (♦). Results of the linear mixed model are presented with p-values for
the main effect year (Y) in vaccinated (V+) and non-vaccinated herds (V−) as well as the interaction term between the year and vaccination status of the
farm (Y*V). The trend of change in the two groups of herds is given with lines (solid line for vaccinated herds and dashed line for non-vaccinated herds) of
average fitted values obtained from the model.
pre-vaccination period. From our previous studies we
reported a significant association between high occurrence
of respiratory disease in unweaned calves and the presence
of BHV-1 among cows (Raaperi et al., 2012b). However,
BHV-1 was not significantly associated with high respiratory disease occurrence among heifers (Raaperi et al.,
2012b) or cows (Raaperi et al., 2012c). Unfortunately there
is no obligation to insert disease incidence data into the
EARC database, so we could not test the change of respiratory disease incidence statistically.
In vaccinated herds the overall culling rate of youngstock increased, whereas it remained unchanged in
non-vaccinated herds. Still, in vaccinated herds the average culling rate was lower than in non-vaccinated herds in
the beginning of the study period and reached the same
level by the end of it (year 2012) (Fig. 2A). The culling
Please cite this article in press as: Raaperi, K., et al., Effect of vaccination against bovine herpesvirus
1 with inactivated gE-negative marker vaccines on the health of dairy cattle herds. PREVET (2015),
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7
Table 3
Results of farmer’s opinion about the change in herd health during BHV-1 vaccination period compared to pre-vaccination period.
Question
Answer
Replies (n/n total)
Farm V+
Change in calf
respiratory disease
incidence
Increased
Decreased
Remained the same
Don’t know
1/6
5/6
0
0
II
I, III, IV, V, VII
Change in heifer (6
months to calving)
respiratory disease
incidence
Increased
Decreased
Remained the same
Don’t know
0
6/6
0
0
Change in respiratory
disease incidence
among cows
Increased
Decreased
Remained the same
Don’t know
0
4/6
1/6
1/6
Change in calf
mortality
Increased
Decreased
Remained the same
Don’t know
0
5/6
0
1/6
Change in heifer
abortion incidence
Increased
Decreased
Remained the same
Don’t know
0
1/6
1/6
4/6
II
VII
I, III, IV, V
Change in cow
abortion incidence
Increased
Decreased
Remained the same
Don’t know
0
2/6
2/6
2/6
III, IV
II, VII
I, V
Change in heifer/cow
reproduction
performance
Improved
Worsened
Remained the same
Don’t know
2/6
0
3/6
1/6
II, III
Change in milk
production
Increased
Decreased
Remained the same
Don’t know
3/6
0
0
3/6
II, III, VII
Change in treatment
costs (antibacterial
drugs)
Increased
Decreased
Remained the same
Don’t know
2/6
2/6
1/6
1/6
II, III
I, IV
V
VII
I, II, III, IV, V, VII
I, II, IV, VII
V
III
I, II, III, V, VII
IV
I, V, VII
IV
I, IV, V
V+ – vaccinated.
rate of youngstock due to respiratory disease remained
statistically unchanged in vaccinated herds but increased
in non-vaccinated herds during six study years (Fig. 2B).
This indicates that in vaccinated herds youngstock was
culled more often for other reasons than respiratory disease. We analysed culling data for all other culling reasons
and only found that the culling rate due to metabolic disorders increased in the second, third and fourth year of
the vaccination period followed by a decline. After that it
remained at the same level as it was among non-vaccinated
herds at the end of the study period (data not shown). EARC
discriminates between metabolic disorders and digestive
disorders in their youngstock culling database. Unfortunately there are no instructions available for the farmer
by how to interpret different culling reasons. The average culling age due to metabolic and digestive disorders
among youngstock was six months and one month, respectively, in the EARC Annual Synopsis 2012. Based on that,
we can assume that culling due to metabolic disorders
is related with conditions leading to inadequate growth,
whereas mortality or culling due to calf diarrhoea can be
excluded. As most of the farmers claimed that calf mortality decreased after vaccination we can assume that more
heifers stayed in the herd and the farmer could probably do
more voluntary culling among youngstock, excluding the
inadequately growing heifers or animals with phenotype
imperfection.
Culling cows due to respiratory disease showed an
increasing trend in non-vaccinated herds but no changes
were ascertained among vaccinated herds (Fig. 2C). It is
difficult to state whether or not this is linked to BHV-1. We
did not carry out any investigations in the non-vaccinated
herds and are unable to explain what is actually behind that
trend.
We also asked about the change in treatment costs
(antimicrobial agents) in vaccinated herds during the vaccination period. Decrease in treatment costs was declared
by two farmers (V+ I and IV); two farms stated they
experienced an increase in treatment costs (V+ II and
III). We did not ask the cause of treatment; therefore
changes in treatment costs cannot be attributed to a specific
cause.
Please cite this article in press as: Raaperi, K., et al., Effect of vaccination against bovine herpesvirus
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8
Youngstock culling rate (%)
A
40
V+
V-
30
Y(V-)
Y(V+)
Y*V
p = 0.535
p = 0.035
p = 0.054
2009
2010
20
10
0
2007
2008
2011
2012
2011
2012
Year
Youngstock culling rate (%)
due to respiratory disease
B
7
V+
V-
6
Y(V-)
Y(V+)
Y*V
p < 0.001
p = 0.461
p = 0.003
2009
2010
5
4
3
2
1
0
2007
2008
Year
C
Cow culling rate (%)
due to respiratory disease
4
V+
V-
3
Y(V-)
Y(V+)
Y*V
p = 0.054
p = 0.374
p = 0.043
2
1
0
2007
2008
2009
2010
2011
2012
Year
Fig. 2. Culling rates in herds of a longitudinal bovine herpesvirus 1 vaccination study during years 2007–2012 in Estonia. Graph points represent
the raw data in vaccinated () and non-vaccinated herds (♦). Results of
the linear mixed model (A) and mixed effect negative binomial model (B
and C) are presented with p-values for the main effect year (Y) in vaccinated (V+) and non-vaccinated herds (V−) as well as the interaction term
between the year and vaccination status of the farm (Y*V). The trend of
change in the two groups of herds is given with lines (solid line for vaccinated herds and dashed line for non-vaccinated herds) of average fitted
values obtained from the model.
4.1.2. Reproduction and milk production
According to the farmers’ opinions, the overall reproduction status among heifers and cows improved or
remained the same after the beginning of the vaccination programme. Farmers evaluated the change in abortion
incidence differently, but none of them claimed that the
abortion incidence had increased. The insemination index
showed an increasing trend and the first service conception
rate decreased significantly in non-vaccinated herds but
remained unchanged in vaccinated herds (Fig. 1C and E).
The length of the dry period shortened considerably in vaccinated herds, whereas it remained statistically unchanged
and longer in non-vaccinated herds (Fig. 1D). Studies have
shown improvement in reproductive performance with a
shorter dry period in multiparous animals. Due to shorter
dry periods, the postpartum negative energy balance is
improved, resulting in fewer days to first ovulation and
a greater success of artificial insemination (Watters et al.,
2009; Grummer et al., 2010; Mansfeld et al., 2012). This
may have an impact on the overall calving interval, which
showed a decreasing trend in the vaccinated herds over
the years, whereas an adverse trend was observed in nonvaccinated herds (Fig. 1A).
A negative effect of BHV-1 infection on milk production has been reported from earlier outbreak investigations
(Hage et al., 1998; van Schaik et al., 1999). In the simulation model by Vonk Noordegraaf et al. (1998) the average
decrease in milk production of gE-positive cows was considered to be about 150 kg per year, which is about 2%.
Our results show that inhibiting virus circulation within
the herd and keeping the young replacement cows free
of BHV-1 infection results in an increase in milk productivity on average 145.30 kg/year (95% CI = −6.11, 296.71,
p = 0.065) compared to that in non-vaccinated herds. This
may also be the consequence of shorter dry periods and
calving intervals, leading to higher number of days in milk
with concurrent increase in milk production (Kuhn et al.,
2006; Bello et al., 2012).
4.1.3. Validity and bias of the study
The limited sample size has lowered the power of
the study; therefore some relationships might have been
insignificant. Herds participating the study were large with
more than 400 dairy cows. The total number of herds in
this herd size category (herds with >400 cows) was 59
in year 2010 in Estonia (about 1% of all dairy cow herds)
(Estonian Animal Register, 2010). Thus the study sample
(24% of largest herds) may be considered to represent well
this subpopulation of herds. Also, 38% of all dairy cows of
Estonia were kept in these 59 herds (Estonian Animal Register, 2010) meaning the study covered substantial part of
all dairy cows in the country. Consequently, the results of
this study can be extrapolated mainly to larger herds with
intensive production systems and relatively high productivity.
All herds originated from the same source population
which consist of herds randomly selected from the list of
all herds with more than 400 cows and positive BHV-1
antibody test result in 2004 which participated the prevalence study in 2006–2008 (Raaperi et al., 2010). The study
included all herds that volunteered to start vaccinating
Please cite this article in press as: Raaperi, K., et al., Effect of vaccination against bovine herpesvirus
1 with inactivated gE-negative marker vaccines on the health of dairy cattle herds. PREVET (2015),
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after the prevalence study (Raaperi et al., 2010) and nonvaccinated herds were matched with vaccinated herds
according to herd and management characteristics. Therefore the study herds should well reflect the source and
target population and selection bias is reduced to minimum. Time gap of up to two years occurred between
measurement of the initial prevalence and start of the
vaccination programme, therefore the initial BHV-1 prevalence estimates may be somewhat biased. Still, the process
of endemic infection was continuous in all study herds
during that intermediary time and the probability of considerable changes in within-herd prevalence of BHV-1 is
the same for all fourteen herds. However, herd BVDV status was one of the matching criterions and five herds were
BVDV negative at the time the first farm inspection and
sampling took place. Some herds might have introduced
the infection during that time gap causing misclassification bias of the herd BVDV status turning to concurrent
selection bias in the matching process.
Vaccinated herds may differ from non-vaccinated herds
as well as being more prone to make improvements also
in other animal husbandry practices, e.g. feeding, keeping
management, controlling other infectious diseases; as well
as attitude, education and awareness of the farm owner
or manager. Therefore some confounding bias may still
remain even after matching on herd variables. Also, due to
the limited number of possible non-vaccinated herds available, we could not match herds perfectly in all aspects (milk
production level, BVDV status, etc.) (Table 1).
Vaccination was interrupted in the ‘V+ V’ farm due to
financial problems from spring 2012 to spring 2013. We
don’t expect the effect of vaccination to wane sharply after
a five-year vaccination period and no dramatic changes in
herd health data were noticed; therefore we still included
the herd in our study. Due to communication difficulties, questionnaire data were not received from the ‘V+ VI’
herd, limiting our conclusions about the farmer’s opinion
in the change of herd health. Despite that, confirmation
about the regular continuity of the vaccination programme
was gained after communication with the veterinarian
employed by that farm, allowing us to include the farm
data in the statistical analysis.
5. Conclusions
Our findings indicate that the BHV-1 infection may have
clinical significance for Estonian dairy cattle herds and
is most probably a limiting factor for dairy production.
Although sample size of this study was relatively small,
significant relationships were detected between BHV-1
vaccination and productivity parameters. Larger number
of herds of different size participating in a study would
allow us to evaluate more broadly the impacts of the BHV-1
control on herd health and productivity in different production systems. This information is especially valuable for
farmers and veterinary advisors from countries with voluntary BHV-1 control programmes, as improvement of herd
health and productivity are the major incentives to invest
in a rather costly, laborious and long-term disease control
programme.
9
Conflict of interest statement
The authors declare that they have no financial or personal relationships with other people or organisations that
could inappropriately influence the results of this study.
Acknowledgements
This research was supported financially by the
Estonian Ministry of Agriculture (Research contract 34-23
2006–2008) and by Institutional Research Funding (IUT81) of the Estonian Ministry of Education and Research. The
authors thank the farmers and veterinarians participating
in the study and the Estonian Animal Recording Centre for
providing the data.
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