BOVINE VIRAL DIARRHEA VIRUS 0749-0720/95 $0.00 + .

20

EPIDEMIOLOGY OF BOVINE
VIRAL DIARRHEA VIRUS
Hans Houe, DVM, PhD

Experimental studies on bovine viral diarrhea virus (BVDV) have

shown that cattle can be infected in two different ways. Postnatal infec-
tion of animals that have not been exposed previously (acute infection)
causes a transient viremia followed by antibody production. Fetal infec-
tion in early pregnancy, on the other hand, will induce immunotolerance
to BVDV,61 and the calf is later born as persistently infected (PI) with
BVDV and remains so for the rest of its life. It is among these PI animals
that mucosal disease (MD) may occur.l3, 18 Because of these clarifications
it became easier to set up sound epidemiologic studies.
When investigating possible ways of transmission of infection in
field studies, it is crucial to know whether PI animals are present in the
herd. PI animals playa key role in the epidemiology of infection because
they are probably the most important source of infection. Whereas the
importance of PI animals for transmission of BVDV is well established,
other sources and routes of transmission other than direct contact are
less clear. Some studies provide evidence that spread of infection does
occur in the absence of PI animals, but the widespread occurrence of PI
animals has often made the transmission of infection by less defined
mechanisms difficult to investigate.
The efficacy of PI animals transmitting the infection at the herd
level might be used in the identification of herds with PI animals. Thus
determination of antibodies among a few animals or determination of
antibody titer in bulk milk will give indirect evidence of the presence of
PI animals, because PI animals show their presence by infecting most
other animals in the herd.

From the Department of Clinical Studies, The Royal Veterinary and Agricultural Univer-
sity, Frederiksberg, Denmark

VETERINARY CLINICS OF NORTH AMERICA: FOOD ANIMAL PRACTICE

VOLUME 11 • NUMBER 3 • NOVEMBER 1995 521

522 HOVE

This article outlines the geographical distribution of infection and

offers possible explanations for differences in occurrence of infection.
Experimental studies on possible means of transmission are described.
Through evaluation of different field studies' typical transmission pat-
terns and time sequence for the occurrence of clinical symptoms are
characterized. Furthermore, the use of serology in the surveillance of
infection is summarized and, finally, the economical importance of
BVDV infections is discussed.

GEOGRAPHIC DISTRIBUTION: PREVALENCE AND

INCIDENCE OF INFECTION

Prevalence of Infected Animals

BVDV infections appear to be widespread in all cattle-raising coun-

tries, although some differences between regions and countries are pres-
ent (Table 1). The prevalence of BVDV infections can be expressed as
the prevalence of antibody carriers or as the prevalence of PI animals.
Antibody titers against BVDV obtained by natural infection usually
decrease very slowly,19 and most often once an animal is infected, it will
be antibody positive for the rest of its life. Except for areas using
vaccination, therefore, the prevalence of antibody carriers reflects the
proportions of animals previously exposed to BVDV at some point of
life. The number of PI animals produced is determined by the incidence
of acute infections among antibody-negative animals in early pregnancy
and by vertical transmission from PI animals themselves. The prevalence

Table 1. PREVALENCE OF BVDV INFECTIONS IN VARIOUS PARTS OF THE WORLD

Prevalence

Past Antibody-
No. of No. of Evidence Positive
Country Animals Herds Animals of BVDV Viremic/PI* (%) References

UK 1593 133 Calves/adults No NK 62 35

UK 924 NK Calves/adults No 0.8/0.4 NK 51
UK 3151 NK NK Yes 1.8/NK NK 28
UK 18,759 NK NK Yes NK 65 28
Germany 2317 >1000 Adults No 0.9/NK NK 54
Denmark 1332 NK Adults No 0.9/NK 78 63
Denmark 2570 19 Whole herds No 1.4/1.1 64 45
Sweden 711 114 Breeding heifers No 1.7/1.3 41 1
Sweden 413 15 Adults No NK 46 69
Norway 1133 187 Adults No NK 19 59
US 3157 66 Calves/adults Yes 1.9/1.7 89 12
US 5481 20 Whole herds No 0.11/0.13 NK 43
USt 794 5 Whole herds No 0/0 29 43

Whole herds = All animals in the herds have been tested; NK = not known.
*Not all viremic animals were retested; therefore, the true prevalence of PI animals might have
been higher on some occasions (see text for details).
tFive herds without PI animals and without any vaccination program.
 EPIDEMIOLOGY OF BVDV 523

of PI animals then follows from the number of PI animals produced,

reduced by the number of PI fetuses aborted and the number of PI
animals dying. A good association has been shown between the inci-
dence of infection in early pregnancy and the prevalence of PI animals
younger than 1 year of age. 45
Because many acute infections will not result in PI animals because
the cow is not at the critical stage of gestation « 100-125 days) and
because naturally acquired immunity is considered to prevent fetal
infection later,71 the prevalence of antibody carriers is inherently much
higher than the prevalence of PI animals in the cattle population.
A survey of 1593 cattle sera from 133 herds in England and Wales
showed that 62.5% of the animals had serum neutralizing (SN) antibod-
ies against BVDV. The prevalence in different regions varied between
43% and 79%. 35 Also in the United Kingdom (UK), a prevalence study
of BVDV among apparently normal cattle showed viremia in 0.8% of 924
animals, but one animal could not be retested and two seroconverted;
therefore, a total of 0.4% proved to be PI.51 Another survey from the UK
showed 1.8% viremic animals among 3151 animals that were tested as
part of preventive screening programs in herds with a suspected prob-
lem of BVDV infection, and the seroprevalence among 18,759 samples
was 64.9%. 28
Among 1332 normal randomly collected cattle sera from two slaugh-
terhouses in Denmark, 78% were SN-antibody positive, and BVDV was
detected in 0.9% of the animals. 63 A study of all 2570 animals in 19 herds
considered to be representative of Danish dairy herds showed that 37
(1.4%) of the animals were viremic, 28 of which (1.1%) proved to be PI,
and 64% were antibody positive. 45
In Sweden, examination of 711 heifers selected for artificial insemi-
nation showed viremia in 12 animals (1.7%), 9 of which (1.3%) were
retested and proved to be PI.1 SN-antibodies were detected in 41 of %

the serum samples. The prevalence of antibody carriers varied from 76%
in the south with more intensive dairy production to 21 % in the northern
part of Sweden with low cattle density. Examination of all 413 cows in
15 randomly selected herds in Sweden showed 45.5% antibody-positive
animals. 69
A survey of 1133 dairy cows from 187 herds in Norway showed
SN-antibodies in 18.5%. The prevalence was lowest in the northern
(6.50/0) and highest in the south-eastern (24.2%) part of the country. 59
Neither the UK, Denmark, Sweden, nor Norway use vaccination in the
control programs.
In the United States (US), examination of 3157 animals from 66
herds, approximately one half of which had past evidence of BVDV
infection, showed 1.7% PI animals and 89% antibody-positive animals. 12
All the PI animals in this survey came from only two herds, one of
which had a history of BVDV infection. Another four herds contained a
total of six viremic animals, but retesting to confirm PI was not possible.
Testing of all animals in 20 randomly selected dairy herds enrolled in
the Dairy Herd Improvement Association in two countries in central
524 HOVE

Michigan showed 0.13% PI animals among 5481 animals tested. 43 The

prevalence data are summarized in Table l.
Many of these surveys were more or less biased towards examina-
tions of animals from herds with recent clinical outbreak of BVDV
infection or towards selected age groups of animals. It seems that the
prevalence of BVDV infections, however, may reach a maximum level
of 2% PI animals and 65% to 75% of the population being antibody
positive when test sera are sampled from herds without past evidence
of BVDV infection. It seems that the infection is self limiting. If the
incidence of infection becomes very high then more and more animals
acquire immunity before breeding and fewer PI animals are born. A
reduction in the number of PI animals then cause the incidence of
infection to decrease again.

Prevalence of Infected Herds

To elucidate the prevalence of infected herds either based on pres-

ence of antibody-positive animals or the presence of PI animals, the
most optimum method is to perform whole herd screening. This is a
very laborious and expensive procedure, however, and has only been
performed on a few occasions.
Whole herd testing in Denmark showed PI animals in 10 of 19 herds
(53%).45 Antibody-positive animals were detected in all 19 herds (100%).
A similar study in the US only showed PI animals in 3 of 20 herds
(15%).43 Antibody carriers were detected in four of five herds not using
vaccination (80 %).
A survey in Denmark based on a serologic screening test of 10
young stock per herd showed that 18 of 42 herds (43%) probably con-
tained PI animals because almost all animals in the screening sample
were antibody positive. 41
In a study conducted in Sweden and testing only cows, antibody
carriers were detected in 11 of 15 herds (73%).69 Also in Sweden 103 of
123 dairy herds (86%) had BVDV antibodies in bulk tank milk, whereas
in Finland only 9 of 291 dairy herds (3%) had antibodies in bulk tank
milk. 68
In the UK, examination of 380 submissions of 10 or more samples
from each herd for serology showed antibody carriers in 361 herds
(95% ).28 Thus, in most, but not all countries, the vast majority of herds
have experienced BVDV infection within recent years.

Incidence of Infection

From the age distribution of antibody carriers the annual incidence

of infection in Denmark has been calculated as 34%. 45
During a 3-year study period, eight of nine Danish herds previously
demonstrated to be without PI animals had experienced new infections
corresponding to an annual herd incidence risk of infection of 52%. 47
 EPIDEMIOLOGY OF BVDV 525

Repeated examination of bulk milk antibody level 1 year apart in

105 Swedish dairy herds showed significant increase in antibody level
in 5 of 43 herds (12%) with an initial low antibody leve1. 68

Determinants for Differences in Geographic

Distribution

Most of the prevalence data from various countries are not directly
comparable because of different criteria for selection of animals. Further,
some of the variation in prevalence data between regions may be the
result of random variation because investigations included only a limited
number of animals and herds. However, there undoubtedly are true
differences in prevalence and incidence of infection between certain
countries and regions. The reasons for these differences can only be
speculated. It seems rather obvious to anticipate that the higher preva-
lence of infection in southern Norway and Sweden compared with the
northern region and the higher prevalence in Denmark compared with
Norway and Sweden can simply be explained by the fact that the
prevalence of infection tends to increase along with an increased density
of cattle in the area. Also herd size could playa role. The four countries
(Finland, Norway, Sweden, and Denmark) have an increasing herd size
in the mentioned order of countries and also an increasing prevalence
of infection. It seems reasonable to assume that a larger herd size is
more easily infected than a small herd size (other factors being equal).
An infected herd in an area with large herds has higher impact on the
overall prevalence of infection compared with infection of a herd in an
area with small herd sizes, because once a herd is infected most animals
in the herd will most likely become infected sooner or later. This effect
of herd size is not obvious when, for example, Denmark is compared
with Michigan. Michigan has a low prevalence of infection but larger
herds compared with Denmark. However, the problem is complex and
each determinant should not be evaluated separately from other deter-
minants. There are many other important differences between Michigan
and Denmark. When relevant factors for occurrence of infection in the
two areas are compared, most are in favor of a lower prevalence of
infection in Michigan. First, many herds in Michigan use BVDV vaccines
to control spread of infection. Further, the concentration of cattle and
cattle herds is lower in Michigan, and pasturing of animals is used to a
lesser extent. The common policy of selling bull calves shortly after birth
from Michigan dairy herds will reduce the number of PI animals and
thus reduce infection pressure on pregnant animals within dairy herds.
Finally, it is a more common practice that young stock are housed on a
separate farm, again reducing the amount of infection from young stock
to pregnant animals in the cow barn. Many circumstances can account
for differences in epidemiologic patterns observed between areas. If all
relevant determinants were obtained in a number of areas with preva-
lence surveys, it might be possible by mathematic modelling to rank
526 HOVE

the epid,emiologic and other determinants in accordance to their effect

on prevalence of infection.

SOURCES OF INFECTION AND METHODS OF

TRANSMISSION

Sources of Infection

PI cattle are considered the most important source of BVDV infec-

tions. The amount of virus in these animals is extremely high. Serum
samples diluted up to 106 may still yield virus when examined by
virus isolation techniques. Is PI animals shed large amount of virus
continuously in secretions and excretions such as nasal discharge, saliva,
semen, urine, feces, tears, and milk.Is, 22, 85 In PI bulls virus titers of 107
have been found in semen.72
Also, acute infected cattle are sources of infection. Following acute
infection, virus usually is excreted from day 4 until day 10, but virus
may be excreted for a longer period. 19 The acutely infected animals also
shed virus in most excretions and secretions. The amount of virus,
however, is much lower than in PI animals. Experimental infection of
five bulls yielded virus titers in semen from 1:5 to 1:75. 53
Apart from cattle, BVDV has been isolated from many other rumi-
nants including sheep, goats, and many captive or free-living species
and these species, therefore, are also considered potential sources of
infection. Thus, virus transmission between sheep and cattle has been
demonstrated. 20, 29, 30 BVDV has also been isolated from pigs. ss,88 Their
importance as source of infection, however, remains to be clarified.
BVDV among other species than cattle are dealt with in other articles in
this issue.

Methods of Transmission

The methods of transmission can be classified into vertical or hori-

zontal transmission. Vertical transmission is from one generation to the
next. Hence, it can be said that all PI animals are produced by vertical
transmission. But, in most cases, the vertical transmission is preceded
by horizontal transmission to the dam, and during the following acute
infection of the dam, the virus crosses the placenta and infects the
fetus. Horizontal and vertical transmission, therefore, often are closely
associated and sometimes difficult to differentiate. In this article, only
transmission to fetuses through infected semen and infected embryos
and transmission from PI dams to PI fetuses will be described as vertical
transmission.
 EPIDEMIOLOGY OF BVDV 527

Vertical Transmission
As previously mentioned, BVDV is excreted in semen in both
acutely infected and PI bulls. Antibody-negative cattle that are insemi-
nated by infected semen will be infected, but the production of a PI
fetus occurs rarely by this route. By inseminating 12 antibody-negative
heifers with semen from a PI bull all heifers seroconverted within 2
weeks. All heifers became pregnant and delivered live calves. Only one
of the calves became PI.65 It is unclear whether the transmission is
transmitted vertically from the bull or it is initially transmitted by
horizontal transmission to the dam and then transmission back to the
embryo. Testing of 1538 bulls in four artificial insemination centers
showed 12 PI bulls. 50 Bulls should always be tested and found virus
negative before they are used for artificial insemination.
Despite high mortality among PI animals40 many will reach adult-
hood and reproduce. Calves delivered from PI dams have so far always
been demonstrated to be PI. Thus, family lines of PI animals in several
generations may occur.38, 78, 85 Vertical transmission will also occur after
embryo transfer if the recipient is PI. If the donor cow is PI, BVDV is
present at high levels in the uterine environment,15 and BVDV will be
transmitted with the embryo if proper washing procedures are not
followed. Again, the mechanism initially may be by horizontal transmis-
sion to the dam followed by transmission back to the embryo. If proper
washing procedures of embryos from PI animals are performed, it is
possible to prevent them from later becoming PI calves. 3,91

Horizontal Transmission
Horizontal transmission can be either direct or indirect. Direct con-
tact between susceptible animals and PI animals is an important way of
transmission of infection between animals, presumably most efficient by
nose-to-nose contact. 89 There is some uncertainty about the possibilities
of air transmission. Air transmission over short distances seems likely,
although it has not been proved experimentally. In herds with PI animals
in which all animals were kept in the same building or in buildings only
separated by doors, a rapid spread of infection was observed. 49 When
cattle are housed at greater distances from PI animals, however, the
spread of infection is slow or absent. 4,93 Also, transmission from acutely
infected animals occurs, but with much less efficiency than from PI
animals. Some experimental studies showed no spread of infection from
acutely infected animals to susceptible animals even though they were
in close contact. 65 However, seroconversions among assembled cattle
without presence of PI animals indicate that transmission from acutely
infected animals sometimes does occur. 64
Although transmission through semen occasionally may produce a
PI calf by vertical transmission, semen may be an important way of
horizontal transmission to the cow. The acutely infected cow may then
528 HOVE

pass the infection on to nearby standing cows, some of which may be

in early pregnancy.
Unlike direct transmission, indirect transmission involves an inter-
mediate vehicle that transmits the pathogen between infected and sus-
ceptible animals. The possibilities of indirect transmission depends on
the stability of the virus outside the host. In the laboratory, BVDV has
been found stable at temperatures below 10°C and in the pH range 3 to
9. 26 The time required for inactivation of BVDV in cattle slurry was 3
hours at 35°C, 3 days at 20°C, and 3 weeks at 5°C?
Vaccination of pregnant seronegative cattle with live BVDV vaccines
can result in transplacental infection of the fetus with the same conse-
quences as natural BVDV infections including PI.56 Further, live virus
vaccines have the potential of inducing mucosal disease when used on
PI animals because some live virus vaccines contain the cytopathogenic
BVDV.25, 74 Spread of infection by vaccines contaminated with BVDV
also has been reported. 57,58 BVDV may be transmitted during embryo
transfer if the wash fluids are contaminated by BVDV. Commercially
prepared fetal calf serum has often been a source of BVDV.82 These
reports have prompted the safety procedures to be improved, and trans-
mission by these means is probably becoming less frequent.
Attempts with experimental transmission of BVDV by blood feeding
flies demonstrated that it was possible to isolate virus from such flies
up to 96 hours after they had foraged on a PI animal. Further, it was
shown that transmission between a PI animal and susceptible animals
was possible when 50 flies were fed on the PI animal for 5 minutes and
15 minutes later fed on susceptible animals. 86 There also is experimental
evidence that BVDV can be transmitted indirectly to cattle by humans
using various instruments and equipment. It was shown that reusing a
19-9auge needle on susceptible animals 3 minutes after the needle had
been used on a PI animal could transmit the infection. Re-using a nose
tong within 3 minutes after it had been used on a PI animal could also
transmit the infection. 32 Other means of indirect transmission such as
clothing are considered possible. l l
Except for direct contact with PI animals, the practical importance
of these other mentioned transmission routes is difficult to evaluate. For
example, do blood feeding flies play an important role in transmission
of infection?
To elucidate the importance of transmission routes other than direct
contact with PI animals, the next section describes and compares trans-
mission of BVDV in different field studies, both with and without the
presence of PI animals.

TRANSMISSION PATTERNS OF BVDV INFECTION

Introduction of the Infection into the Herd

It is well documented that the purchase of a PI animal or a pregnant
animal carrying a PI fetus will introduce BVDV into a herd?9,81 The
 EPIDEMIOLOGY OF BVDV 529

number of new introductions of infection, however, seem far greater

than can be explained from direct purchase of PI animals. 47 Further, the
occurrence of PI animals in separated age groups indicates that the
initial introduction of infection is by other routes than direct introduction
of a PI animal. This is illustrated in Figure 1. The figure shows the time
sequence of delivery of PI animals relative to the oldest PI animal in the
herds. Thus, PI animals are often born in two separate age groups, i.e.,
an initial smaller group of PI animals followed by a second larger group
being born approximately 6 months after the first group. This was the
typical pattern in at least 10 of 22 herds (Fig. 1).38 Similar patterns of the
occurrence of PI animals have been described in case reports. 10, 67 As PI
animals, except for PI animals born by PI dams, are produced by
infection of the dam in the first trimester of pregnancy, the birth of PI
animals will reflect the infection among the dams 6 to 9 months pre-
viously. Thus, the initial acute infection in the herds shown in Figure 1
had been of short duration and only involving a few animals before the
transmission stopped. The initial spread of infection, therefore, was most
likely not from direct introduction of PI animals. Still, the introduction
might have been from a PI animal if only part of the herd had been
exposed to a PI animal. There is evidence that over-the-fence contact
with a PI animal from a neighboring herd can introduce the infection,8o
and this could cause a more limited spread of infection. Thus it seems
that the infection is introduced either as PI animals shedding larger
amount of virus or from one of the other routes, which would be

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MONTHS AFTER BIRTH OF OLDEST PI ANIMAL

Figure 1. Incidence of PI animals and non-PI animals born after the oldest PI animal in
each of 10 herds in which the range of the age of PI animals was more than 6 months.
The oldest PI animal from each herd is included in the figure in month 1. Asterisk indicates
PI animals born by PI dams. White bar = non-PI animals; black bar = PI animals. (From
Houe H: Age distribution of animals persistently infected with bovine virus diarrhea virus in
twenty-two Danish dairy herds. Can J Vet Res 56:194-198, 1992; with permission.)
530 HOVE

associated with less viral shedding. Both ways of introduction seem

fairly common.

Perpetuation of Infection Within the Herd

Once the herd is infected, the transmission of BVDV in cattle herds

may continue for a long time before all or almost all animals are infected
and the herd becomes immune. The speed of the continued transmission
depends on whether the transmission is perpetuated from (1) an ongoing
acute infection among animals in the herd or from (2) a PI animal. When
transmission studies are performed, the situation may be blurred by a
second introduction of the virus. Thus, it might be difficult to distinguish
an apparently slow ongoing acute infection from a situation with two
or three separate introductions of the virus.
The transmission of infection within herds also depends on how
close the animals are housed together. Further, the strain of the virus is
important. Some strains seem to contribute to respiratory disease either
directly or by increasing susceptibility to other infections.7s, 76, 77 This may
cause coughing among acutely infected animals, which will increase the
dissemination of BVDV.

Spread of Infection in Herds Without PI Animals

From Figure 1 it seems that the initial acute infection in the 10 herds
had been of short duration because of the time lag between the first and
the second group of PI animals. However, other studies have indicated
a slow and prolonged spread of infection among acutely infected ani-
mals. In a dairy herd in which the adult and young stock were housed
and pastured separately the virus continued to circulate among lactating
cows for 2.5 years, although they had no direct contact with PI cattle. 66
In another report, it took 2 years after the initial outbreak before all but
three of the breeding stock had been infected. 6 Later investigations in
the same herd showed that after all viremic animals were removed, a
few animals were infected over the next 2 years showing that the virus
continued to circulate in the herd, although the efficiency of virus spread
was poor. 5
Thus, in the absence of PI animals there is potential for continued
transmission either slowly as ongoing acute infection as suggested
earliers,66 or the infection could have been reintroduced by indirect
contact with PI animals as discussed by others.5 The possibility of
excretion of virus from latently infected animals could explain the con-
tinued circulation of virus. However, there seems to be little evidence of
latency in BVDV infections. 17
The possible continuation of acute infection when no PI animals are
present is critical in any control program based on identification and
removal of the PI animals. Further discussion of this matter will be
presented in the article on control in this issue.
 EPIDEMIOLOGY OF BVDV 531

Spread of Infection in Herds With PI Animals

When PI animals are present, the infection usually spreads rapidly
to most animals in the herd,81,87 especially in herds in which animals are
housed with close contact. In 10 herds with PI animals, 87% of all cattle
were antibody positive compared with 43% in nine herds without PI
animals. When 65 antibody-negative and non-viremic animals in the 10
herds with PI animals were tested 6 months later, 63 had seroconverted
(97%).45 Under grazing conditions, an attack rate from newborn PI ani-
mals of 0.006 to 0.04 per susceptible animal per day were observed
compared with an attack rate of 0.6 from PI animals pastured with
other cattle. 78

Antibody Profiles in Herds at Different Times of the

Infection Cycle
Testing all animals in a herd for BVDV antibodies gives a good
indication of the herd's infection status and the susceptibility to infection
(Figs. 2 through 4). Purchased animals usually should be excluded from
the antibody profiles because the antibody status of a purchased animal
may not reflect the infection status of the herd. Herd A (Fig. 2) had no
PI animals, but a few antibody carriers in various age groups. This is a
characteristic pattern in a herd with recent infection. Antibody carriers
among calves younger than 6 months of age in this and the following
figures are most likely due to colostral transfer. Herd B had only one PI
animal that was 2 months old. The pattern looks like the pattern of a
recent infection as in herd A because the PI calf had not yet had time to
infect remaining antibody-negative animals in this herd. When 23 anti-
body-negative animals were tested 6 months later all had seroconverted.
Herd Chad 10 PI calves that were 3 to 4 months old. All other animals
except three were antibody positive. Figure 3 (herds D and E) shows
examples of antibody profiles in herds without PI animals and appar-
ently no recent introduction of infection. There seems to be an age limit
above which almost all animals were antibody positive, indicating how
long ago there has been PI animals in the herds. As older antibody-
positive cows are replaced by younger antibody-negative breeding ani-
mals, the herd becomes more and more susceptible. Most reinfections in
Denmark and probably elsewhere take place before all antibody-positive
animals in the herd have been ~eplaced with antibody-negative animals.
An example is shown in Figure 4. When purchased animals are excluded
from the figure, there were two antibody-positive animals among a large
age group of otherwise antibody-negative animals. When purchased
animals were included in the antibody profile of this herd, there were
two more antibody-positive animals in the same age group as the first
two. It is possible that these two purchased animals had been acutely
infected just before introduction into this herd; thus, the infection cycle
starts over.
Figure 2. Age distribution of antibody carriers in a herd with recent infection but still without
PI animals (Herd A), a herd with a single two month old PI animal (Herd B) and a herd
with ten PI animals 3-4 months old (Herd C). Data shown in age groups of 3 months. Black
bar = antibody positive; white bar = antibody negative. (Data from Houe H, Meyling A:
Prevalence of bovine virus diarrhoea (BVD) in 19 Danish dairy herds and estimation of
incidence of infection in early pregnancy. Prev Vet Med 11 :9-16, 1991.)
 EPIDEMIOLOGY OF BVDV 533

HERD 0
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HERD E
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Figure 3. Age distribution of antibody carriers in two herds without PI animals. Black bar
= antibody positive; white bar = antibody negative. (From Houe H: Serological analysis
of a small herd sample to predict presence or absence of animals persistently infected with
bovine viral diarrhoea virus (BVDV) in dairy herds. Res Vet Sci 53:320-323, 1992; with
permission.)
534 HOVE

HERD F (NOT INCLUDING PURCHASED ANIMALS)

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HERD F (INCLUDING PURCHASED ANIMALS)

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Figure 4. Age distribution of antibody carriers in a herd without PI animals but apparently
recent infection among 2-year-old animals some of which have been purchased. Black bar
= antibody positive; white bar = antibody negative. (Data from Houe H, Meyling A:
Prevalence of bovine virus diarrhoea (BVD) in 19 Danish dairy herds and estimation of
incidence of infection in early pregnancy. Prev Vet Med 11 :9-16, 1991.)
 EPIDEMIOLOGY OF BVDV 535

SEQUENCE OF CLINICAL MANIFESTATIONS DURING

OUTBREAK AND MORBIDITY AND MORTALITY
AMONG INFECTED ANIMALS

By order of occurrence in cattle herds, the clinical manifestations

can be divided into (1) acute BVDV; (2) reproductive disorders such
as repeat breeding and abortions; (3) birth of malformed, weak, and
undersized calves; (4) unthriftyness among young stock; and (5) muco-
sal disease.
The time sequence and the magnitude of these clinical disorders
show great variability from one herd outbreak to another. Factors con-
tributing to this variation include variations in the transmission pattern,
herd immunity at the time of infection, the pregnancy status of animals
at the time of infection, and difference in virulence among different
BVDV isolates. Despite this variation, some general patterns are still
seen.
In the first description of BVDV infections, the morbidity rate after
acute infection varied between 30% and 90%, and the mortality rate
varied between 4% and 8%. 70 For many years, the common opinion has
been that most acute infections are subclinical. 2,78 Recently, more virulent
strains have been described. In young calves, a hemorrhagic form has
been described/I but more severe forms of the acute infection with high
mortality both among cows and calves recently have been described in
the UK36,23 as well as the US and Canada73 (see article on Clinical
Manifestations, this issue). Although it seems that more virulent BVDV
strains have emerged recently, most acute infections are still considered
to be subclinical.
Often the first signs of infection are reproductive disorders. Infection
of animals by intrauterine infusion at the time of insemination or using
infected semen results in reduced conception rates. 31 ,60 Reduced concep-
tion rate has also been seen after nonvenereal transmission 9 days before
insemination and 4 days after insemination. 62 In some herds, there is a
significant decrease in conception rate for several weeks or even months
after introduction of the virus. 46,81 After the herds have become immune,
the conception rates improve. 48
Usually at least 3 weeks are required from acute infection until
abortion occurs.90 Hereafter, abortion can occur during the following
several months,81,84 and abortion problems often last for approximately
1 year. 64 Figure 5 shows the number of abortions that occurred in four
Danish cattle herds after acute BVDV (as demonstrated by seroconver-
sions in two herds and presence of clinical symptoms in two herds;
clinical signs of acute BVDV occurred over few weeks in these herds).
BVDV was isolated from at least one abortion in each herd. Figure 5
shows a tendency that abortions can be categorized into abortions oc-
curring shortly after acute infection and late abortions occurring several
months after acute infection, which has been suggested by others.34 PI
animals were born approximately 5 to 9 months after the acute infection
in these herds. This is in agreement with the fact that these animals
536 HOVE

20

CIJ
z 15
0
i=
a:
0
m
CC
L1. 10
0
a:
w
m
::E
:J 5
Z

o
1 2 3 4 5 6 7 8 9
NUMBER OF MONTHS AFTER ACUTE BVO

Figure 5. Occurrence of abortions in four dairy herds after clinical outbreak of acute BVDV.
(Data from Houe H: Bovine virus diarrhoea. Epidemiological investigations in Danish dairy
herds. Thesis, Denmark, 1991; and Houe H: Age distribution of animals persistently infected
with bovine virus diarrhea virus in twenty-two Danish dairy herds. Can J Vet Res 56:194-
198, 1992.)

result from infection up to the first 4 months of pregnancy.61 Likewise

as congenital defects and growth retardation are induced in mid-
gestation,24,81 these animals are most often born just before the PI ani-
mals. Thus, the significant increase in neonatal mortality often seen at
the time of birth of PI animals46 can either be PI animals or animals
infected in mid-gestation.
At the herd level, PI animals are often born in groups according to
age (see Fig. 1). Many PI animals are small, lack vigor, and may die
soon after birthJo, 46, 52, 61 However, a considerable number seem to be
clinically normal and may remain unnoticed in the herd. In one study,
15 of 34 PI animals (44%) remained clinically normal until they were
slaughtered. 40 The risk rate of either dying or being slaughtered due to
unthriftyness was calculated as 50% per year in this study.
Most cases of mucosal disease occur in the age range of 6 to 24
months, and mucosal disease is often the first clinical manifestation
that prompts an investigation of BVDV infection. 16, 87 In the screening
performed in Denmark in which PI animals were detected in 10 of 19
herds,45 a diagnosis of BVDV had not been made in any of the herds
before screening. Outbreaks of mucosal disease often begins with the
death of a single animal (index case). After a few weeks, new cases of
mucosal disease are seen.44 When the first case of mucosal disease occurs,
it is often possible to test the herd and slaughter the remaining PI
animals before they develop clinical symptoms and die. Figure 6 shows
the age distribution of PI animals in eight herds with outbreaks of
mucosal disease. A total of 31 animals died, whereas 21 animals were
salvaged for slaughter. If all animals in these herds had been blood
 EPIDEMIOLOGY OF BVDV 537

NUMBER OF ANIMALS
14
• MUCOSAL DISEASE
!a OTHER PI ANIMALS
12

10

o 2 4 6 8 10 12 14 16 18 20 >24
AGE (MONTHS)

Figure 6. Age distribution of PI animals in eight dairy herds with outbreak of mucosal
disease. (Data from Houe H, Lloyd JW, Baker JC: Decision tree analysis of control
strategies in Danish dairy herds with outbreaks of mucosal disease. Prey Vet Med 21: 133-
146, 1994.)

tested immediately after the first case of disease, a total of 32 animals

could have been salvaged for slaughter. 44
Sometimes PI animals will remain clinically normal for an extended
period?8 In one study, 5 of 34 PI animals (15%) were older than 2
years. 40 Three of these already had delivered PI calves. On follow-up
investigation, another four PI calves were born from PI dams. In this
way, PI animals can stay in the herds for several years if no control
measures are taken.
Figure 7 illustrates an outbreak of BVDV infection in a dairy herd.
In the spring of 1989, severe clinical symptoms of acute BVD occurred
among cows. Several cows had diarrhea, fever, and some had respiratory
symptoms. Four cows died. Testing 13 cows for SN-antibody titer on
May 9 and May 23 showed seroconversion among eight cows and a
significant increase in antibody titer in three cows. Blood test of all
animals in the herd showed that two PI animals were born in early May,
which apparently were responsible for the acute infection. During the
following period, seven cows aborted. From 5 to 9 months after the first
PI animals were born, another 17 PI animals were born. When three PI
animals died in June 1990, the remaining PI animals were slaughtered.
In summary, it seems that the possible sequence of events starts
with clinical signs of acute BVDV immediately followed by repeat breed-
ings for a few months and by abortions for several months. At the time
of acute BVDV, PI animals already may be present either as purchased
animals or as young PI animals born into the herd by an earlier limited
spread of infection. Otherwise, PI animals are born 5 to 9 months after
538 HOVE

PI ANIMALS

X
> >< ACUTE INFECTION
><

ABORTIONS

X
X
PI ANIMALS
X DEATH
PREGNANCY PERIOD
X
X

-15 -12 -9 -6 -3 o 3 6 9 12 15

MONTHS
Figure 7. Sequence of events of a BVD outbreak in a dairy herd. The horizontal bars
indicate the in utero period for each fetus aborted and for each PI animal. (Data from Houe
H: Bovine virus diarrhoea. Epidemiological investigations in Danish dairy herds. Thesis,
Denmark, 1991; and Houe H: Age distribution of animals persistently infected with bovine
viral diarrhea virus in twenty-two Danish dairy herds. Can J Vet Res 56:194-198, 1992.)

the clinical signs of acute BVDV (i.e., abortions may still occur when the
PI animals arrive). Some of the PI animals may have congenital defects,
but most congenital defect calves are non-PI and usually are born just
before the PI animals. PI animals have increased susceptibility to other
diseases and increased risk of dying at any time during their life, but
especially develop mucosal disease at the age of 6 to 24 months. This is a
generalized pattern of the BVDV clinical outbreak. When acute infection
occurs over a longer period, the time frames for occurrence of the clinical
manifestations are more blurred. It also should be mentioned that it is
rare to see all the clinical manifestations in the same herd outbreak.
Thus, in herds with many abortions very few or even no PI animals
may be born.37

SURVEILLANCE

As BVDV infections usually are diagnosed several months after the

introduction of infection, various methods of herd surveillance are help-
ful in obtaining an earlier diagnosis. Clinical parameters such as concep-
tion rates and neonatal mortality may be indicators of early infection. 46
Because the clinical parameters show great variability and may look like
other diseases, laboratory examinations always are necessary. Because
 EPIDEMIOLOGY OF BVDV 539

of the high probability of transmission of virus from PI animals, testing

a screening sample of few young stock for antibodies will predict pres-
ence or non-presence of PI animals in the herd with high accuracy. Thus,
in 19 herds in which all animals had undergone blood testing for virus
and antibodies, a screening sample of five animals for antibody analyses
would have classified 18 of the herds (with 98% accuracy) correctly as
to the presence or absence of PI animals. 39 One herd with only one very
young PI animal would not have been detected by this method, because
it takes a few months for the PI animal to infect most of the remaining
herd. A negative screening sample, therefore, should be repeated a few
months later. This method was used in another 42 Danish dairy herds
to test 10 young stock for antibodies. 41 The herds could be categorized
as heavily infected (probably containing PI animals) versus slightly
infected (probably without such animals) (Fig. 8). Blood testing of all
animals in seven of the herds confirmed correct classification by this
method.
In herds using killed vaccine, similar procedure can be used if the
screening sample is tested for SN-antibody titer. Animals exposed to PI
animals will have significant higher SN-antibody titer than animals
vaccinated with killed BVDV vaccine. 42 Also, examination of antibody
content in bulk milk can be useful in the surveillance of dairy herds.
There is a good correlation between the prevalence of antibody-positive
cows and the antibody level in bulk milk. 6s,69 The bulk milk antibody
level, however, is not always useful to distinguish herds with PI animals
from herds without such animals. In herds from which PI animals have

20~----------------------------------------~

en 15
c
a:
w
1:
u.
0 10
a:
w
ID
::!
::)
z 5

o
o 1 2 3 4 5 6 7 8 9 10

NUMBER OF ANTIBODY CARRIERS

Figure 8. Number of antibody carriers among 10 young stock (8-18 months old) in 42
Danish dairy herds. (From Houe H: Bovine virus diarrhoea virus: Detection of Danish dairy
herds with persistently infected animals by means of a screening test of ten young stock.
Prev Vet Med 19:241-248, 1994; with permission.)
540 HOVE

been removed, there may be a considerable time lapse before the anti-
body titers among the cows has decreased significantly or before anti-
body-positive cows have been replaced by antibody-negative cows. In
this situation, the screening sample from young stock for serum antibod-
ies is better because a negative status will be demonstrated as soon as
young stock becomes antibody negative. Also, the possibility of a PI
cow excreting virus in milk and thus causing a decrease in bulk milk
antibody titer needs to be studied. In the surveillance of herds with low
prevalence of antibody carriers, the application of antibody level in bulk
milk is most useful because a new introduction of infection will cause a
significant increase in the number of antibody-positive cows. Still, these
surveillance methods based on antibody detection are not always suit-
able for detection of a very recent infection because sometimes only very
few animals are infected initially. In addition to antibodies, detection of
virus in bulk milk by polymerase chain reaction (PCR) amplification
also has been described. 14 The potential of using PCR in herd diagnosis
of BVDV infection is discussed elsewhere in this issue (see article on
Diagnosis) .

ECONOMIC LOSSES
Herd Level
The large variation in the morbidity and mortality of clinical out-
breaks of BVDV in individual herds is of course reflected in the economic
losses. Only few reports of the economic impact of BVDV can be found
in the literature. In a dairy herd with 67 cows in which the BVDV-
associated damages encompassed two abortions, two dead-borne calves,
three congenital defect calves, two "poor doers," two cases of mucosal
disease, and an additional six PI animals that were slaughtered, the
calculations of the economic losses varied between 1,720£ ($2,655.00)
and 4,115£ ($6,351.00).27 The calculations depended on whether dead
animals were replaced immediately or not and whether only proved
cases or also presumed cases of BVDV associated losses were included
in the calculations.
The economic effect of BVDV infection in 14 Dutch dairy farms was
on average 136 Dfl. ($77.00) per dairy cow with a herd variation from
42 to 285 Dfl. ($24-161) per dairy COW.92
In eight Danish dairy herds with in average 115 animals, the losses
resulting from outbreaks of mucosal disease were calculated to be from
$2,380.00 to $2,980.00 depending on the control measures taken. 44 The
losses in individual herds varied from $743.00 to $5,118.00. Only losses
resulting from mucosal disease were included in the calculations.

National Level
In England, the total national losses have been calculated as 120
million £ ($185 million),83 47 million £ ($73 million)9 and 32 million £
 EPIDEMIOLOGY OF BVDV 541

($49 million).33 With an estimated 4.5 million calvings per year,83 the
losses per million calvings then were 27 million £ ($42 million), 10
million £ ($15 million) and 7 million £ ($11 million), respectively.
In Denmark, the economic losses have been calculated as 13 million
£ ($20 million) per million calvings. 49 The losses from PI animals make
up approximately one half of the economic losses. The annual incidence
risk of infection previously calculated as 34% 45 was included in the
economic model. Sensitivity analyses showed that this infection level
caused losses that are close to the maximum possible losses. The losses
would still increase by an increasing incidence risk to approximately
45%, but once above this level, the losses begin to decrease because
more and more animals are infected before their first pregnancy, and
the heavy losses resulting from fetal infection are avoided.
The models on calculation of economic losses include many assump-
tions and can only be considered rough estimations of the true losses.
The model calculating the total annual national losses in Denmark,
however, showed only little sensitivity to changes in many of the esti-
mated parameters.49 The reason for the low sensitivity is that some
parameters are counterbalancing each other. If for example the risk of
abortion after fetal infection is increased, the losses resulting from abor-
tions increase, but this means that fewer PI animals are born; therefore,
that the losses because of such animals decrease.
Because of the variation in epidemiology between countries, one
should be careful drawing conclusions on economic losses in areas other
than those on which the model was based.

Economical Evaluation of Control Strategies

A computerized decision support system for selection of control
strategy at the herd level has been described. 8 The model was used on
specific herd situations, and the recommended strategy would vary
under different circumstances. No general recommendations, therefore,
were given.
A cost-benefit analysis of three different control strategies: (1) do
nothing, (2) test and eliminate, and (3) vaccinate, test, and eliminate at
the national level was in favor of using a strategy based on strategy
number 3, i.e., vaccination and culling of animals that do not seroconvert
after vaccination. The calculations were performed during a 5-year pe-
riod. 83 No sensitivity analyses, however, were made. For example, a
change of the length of the study period on which the calculations
were based would be interesting. Assuming that the test-and-eliminate
strategy was successful and low-cost surveillance systems were avail-
able, then this strategy would be more favorable when a longer period
was studied.
It is important to stress the significance of differences in epidemiol-
ogy between areas; therefore, the most optimum solution in one area
may not be the best for another area. The decision must be based on a
thorough investigation of the area in question.
542 HOVE

Despite large variation in economic calculations, BVDV undoubt-

edly causes heavy losses in most countries. More detailed calculations
on the cost-benefit of control strategies are needed. As a basis for such
calculations, however, the efficiency of control strategies are crucial. This
will be dealt with elsewhere in this issue (see article on control).

SUMMARY

Prevalence studies around the world show that BVDV is wide-

spread in most cattle raising countries. There are significant differences,
however, in prevalence between areas, probably the result of differences
in cattle population structure and management practice. Direct contact
with PI animals is probably the most important method of transmission
of infection; however, field studies have shown that some limited spread
of infection also occurs in the absence of PI animals. This may be due to
contact with acutely infected animals or contact with other species
infected with BVDV. Different ways of indirect transmission such as
contaminated needles and equipment have been proven experimentally,
and indirect transmission is considered to have some importance. If a
PI animal is introduced directly into a dairy herd, most animals will be
infected within a few months. On many occasions, however, a herd gets
infected by other means than direct introduction of PI animals. In these
cases, the infection is often spread to only a few animals after which the
infection stops. The infection is then reinforced when PI animals are
born. Slow and hence prolonged spread of infection in herds without PI
animals also has been described, but the mechanism is not fully under-
stood. Family lines of PI animals delivering PI calves are fairly common
and can cause the infection to continue for several years.
The clinical manifestations, acute BVDV, reproductive disorders,
birth of malformed, weak and undersized calves, unthrifty PI animals,
and mucosal disease often appear within certain periods. Large varia-
tion, however, can occur between herd outbreaks due to variation in
virulence of the BVDV strain, housing of the cattle, and variation in
transmission patterns.
The extensive transmission of infection from PI animals makes
different surveillance methods possible. Thus testing of a screening
sample of a few young stock for antibodies and determination of anti-
body titer in bulk milk will often give good indication of presence of PI
animals in herds not using BVDV vaccines. In herds using killed vaccine,
determination of antibody titers among few young stock can show the
presence of PI animals.
The high incidence of infection combined with all the different
damages that are seen after BVDV infection cause huge economical
losses, which on a national level in the UK and Denmark (i.e., areas
with widespread occurrence of infection) has been calculated as between
7 and 27 million £ (between $11 and $42 million) per million calvings.
Epidemiologic studies are important as a basis for selection of
 EPIDEMIOLOGY OF BVDV 543

control strategy. Because of the variation in epidemiology between geo-

graphic areas, evaluation of a control strategy in an area preferentially
should be based on epidemiologic studies in the same area.

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Address reprint requests to

Hans Houe, DVM, PhD
Department of Clinical Studies
The Royal Veterinary and Agricultural University
13, Biilowsvej
1870 Frederiksberg C
Denmark