Bovine Viral Diarrhea, Bovine Viral
Diarrhea Virus (BVDV) and related Pestiviruses
Dr. Donal O'Toole
devote a full lecture to this topic because:
It is a
major cause of abortion, perinatal death and weak calves in
Wyoming. It is the single most important virus we deal
with in cattle. In a survey performed by the former
laboratory director, Dr. Woodard, of our case archives, 27% of
all aborted fetuses submitted to the WSVL were infected with
BVDV. Elsewhere in the country the number is lower (1 -
5%) although in
the number is similar to Wyoming's. Finding BVDV in the
fetus does not mean it caused abortion (a hole in the window and
a fly in the room does not mean the fly made the hole in the
window) - we find it in calves that have died of other
conditions, including genetic diseases. But isolating BVDV
from a fetus from your herd means that the agent is circulating.
Odds are that the finding is meaningful.
It can be a source of ill thrift
in older cattle. When they develop a syndrome called
they generally die.
It is a co-factor in pneumonia
(BRD) - please review Dr. Montgomery's notes on respiratory
The virus has a sophisticated
ecology. Understanding it will give you some sense of how
"clever" viruses can be as they attempt to evade mammalian
immune surveillance. It is well adapted so that it causes
little disease in adult animals, yet has a mechanism to cause
vertical (herd-mate to herd-mate) as well as horizontal
infection (dam to fetus).
This disease can be eliminated
regionally or nationally by targeting its Achilles' heel - the
persistently infected cattle
(called PIs). Such cattle can now be
detected and culled. The best laboratory method to do this
is the subject of considerable disagreement among accredited
state laboratories (below) and is the basis of active research.
The agent is widely vaccinated
for. I would like you to understand the limitations as
well as benefits of vaccinating cattle for BVDV. Bottom
line: vaccinate for BVDV, ideally with a modified live virus
product (MLV), but remember that
are more important than vaccination in keeping the virus out of
There is a large amount of
complicated information put out by vaccine companies on BVD.
Not all of it is accurate, to put it mildly. If you have
the disease in your herd, you need a basic understanding of how
this disease works if you are going to control it. Please
do not rely on vaccine companies for the full story. The
complexity of its life cycle and the abuse of scientific
literature should not blind you to the need to look critically
at claims that one vaccine is superior to another.
The US and Canadian approach has
been: vaccinate. Several European countries eschewed
vaccination and instead focused on voluntary (producer-run)
biosecurity and test-and-slaughter programs. Unlike the
US, BVD is now virtually eradicated in several Scandinavian
countries. It's not a coincidence Scandinavia is the natal
home of the Vikings. A report on how this was done,
and test strategies to eliminate the virus in herds, was
recently. Some but not
all of these methods could be used in North America.
viral diarrhea was first recognized in 1946 in New York. At
that time it was one of the few viral diseases identified in cattle
as a cause of diarrhea, hence the inappropriate exclusionary term
bovine viral diarrhea virus.
Obviously, other viruses cause viral
diarrhea in cattle.
pestivirus is a single stranded RNA agent. It is therefore
prone to mutations resulting in multiple variants. The
genotypes based on RNA sequences are the type 1a, 1b and 2.
This is important since most vaccines, until recently, contained
only BVDV 1a (e.g., the NADL and Singer strains). When BVDV-2
was first recognized in Canada, it was associated with a severe,
often fatal disease. Vaccine companies incorporated additional
strains into their products. You will see advertising that
specifies the strain(s) present in a product. It is now clear
that type 2 BVDV is NOT invariably associated with bleeding
disorders. One doesn't have to have a type 2 strain in a
vaccine for cross-protection against type 2 genotypes.
Nevertheless, having attenuated strains that mirror those in the
field is likely to be helpful. The current consensus is
that having both type 1 and type 2 genotypes in the vaccine is
taken from a paper by Dr. Ed Dubovi (J
Vet Diagn Invest 17: 10 - 15,
who has done much of the critical field work on BVDV.
Note that there are multiple genotypes, the principal
ones being 1a, 1b (split between 1b1 and 1b2
subgenotypes) and another other distinct lineages,
genotype 2. There are other type 1 genotypes (c,
d, e, etc). The ones to remember are genotypes 1a,
1b, and 2, since these are the common ones, and are
represented in vaccines.
a relatively fragile virus, since it is enveloped. It
survives poorly in the environment. Its survival strategy is
to infect calves in utero during a particular gestational
window, which is before the immune system can distinguish self from
non-self. The end result is that the fetal calf accepts BVDV
surface antigens as "self" and does not clear the virus. Assuming
the fetal calf survives the initial infection, when it is born it is
infected for life (which may not be long - see below). Such
infected calves are persistently infected (PIs).
eliminating PI calves is the most important way at present to
control BVD in herds.
strains can also be described in terms of biotype: whether
they are cytopathic (CP) or noncytopathic (NCP).
Cytopathic means that one can see the damage it does to cells
infected in the laboratory. Noncytopathic means one can't
recognize this effect. Noncytopathic viruses are an especial
nuisance since infected cells don't look sick, and it is common for
batches of laboratory-grown cells to be contaminated with NCP BVDV.
There have been several spectacular episodes where BVDV got into
viral vaccines and caused a major problem. In truth, whether a
strain of BVDV is cytopathic or noncytopathic is in the eye of the
beholder - it comes down to the experience of the laboratory
technician checking cells, since the effects can be subtle.
The NCP concept is important in that persistently infected calves
have only the NCP strain in their system.
principal effects that we recognize in association with BVDV are:
Abortion - this may occur at any gestational age.
We tend to recognize it in fetal calves at >6 months. This may
reflect the small size of early aborted fetuses, and the difficulty
of finding them on pasture. A typical abortion rate following
introduction of BVDV into a naive herd is 5 - 20%.
As with most infectious agents, the biggest problem tends to be in
the pregnant heifer cohort. The fetus dies 10 - 30 days after
infection and is expelled up to 50 days later. Fetuses may
therefore be rotten and the virus inactivated, so we tell producers
that just because we can't grow the virus does not mean we have
ruled out BVD. When abortions occur, we often have to test
multiple aborted calves before we are confident it is/is not BVD.
Formation of persistently infected (PI) calves. These
are generally infected between 90 and 130 days gestation, just as
immunocompetence (the ability to respond to infection) is
developing. Calves are infected through their dam and across
the placenta. Either their dams are healthy, susceptible
animals that just happen to infected at the "right" time for the
fetus to be infected (this is the case >90% of the time), or they
are persistently infected dams (about 7% of the time). This is
the reason why, when a PI calf is found, the dam should also be
tested: there is about a 1:10 chance she too is PI, and therefore
also needs to be eliminated from the herd.
researchers think they can be infected and formed a little earlier
(60 days and up) and that it is rare for PIs to occur after 100
days. A proportion of infected calves otherwise destined to be
PIs die and are expelled. PI calves may or may not look
abnormal at birth. We recently kept a large group of calves in
the WSVL to establish the best testing method. Most of these
calves did not look too bad, but growth rates were poor.
ONLY THE NCP BIOTYPE OF BVDV RESULTS IN PI CALVES. Some PI
calves have a characteristic "coyote-head" appearance. Yet you
cannot rely on this to spot PI animals.
Persistently infected calves are commonly indistinguishable from
There is substantial
overlap in terms of impacts of BVDV on the fetus.
These are shown above (after
Grooms: 2004, Vet Clin N Am Food
Pract 20(1): 5-19).
A simplification is that disease occurs in the following
sequence gestationally: infertility and early embryonic
death; immunotolerence with formation of PIs; congenital
defects; infection with questionable effects on calf in
first year of life. Abortion may occur at any
time. Experimentally this tends to occur in the
first trimester, but in beef cattle operations the ones
that are recognized are later in gestation (>6 months)
Congenitally defective calves. These occur when they are
infected after about 130 days. Overlap with the PI-formation
stage exists. At 130 days the fetus begins to have a working
immune system, and it is likely that the inflammation that now
becomes possible is responsible for some or all of the tissue damage
that results in a defective newborn calf. The number of
defects is large and essentially any organ system can be affected.
Lesions of the brain and eyes predominate. Congenital defects
were relatively common due to BVDV in my experience in England, and
are beloved by authors of pathology and virology text books due to
their striking nature in the brain, such as cerebellar hypoplasia.
But in Wyoming we see
few overtly defective BVDV calves that make it to full term.
Three other forms are seen: infertility/low conception, due
to death of the oocytes or poor survivability of embryos; early
embryonic death (< 2 months) due to infection of the embryo
and/or damage to the uterine mucosa; and calves that are
congenitally seropositive (= infected in utero and
survived to term) but have few or no abnormalities. Vaccine
company literature tends to emphasize such calves, but
are limited establishing that such calves are a major part of the
disease spectrum of BVD.
BVDV is generally a mild pathogen in
neonatal calves, with some exceptions. Typical BVDV infections
in calves and adults are high morbidity, low mortality affairs.
Generally the virus moves through a herd without being noticed.
Animals have mild fever, a clear nasal discharge, and a transient
drop in white blood cells that signals immunosuppression. The
virus is in their system for 6 - 8 days. Animals recover, and
have a fairly robust immunity.
The exceptions are:
1. BVDV is part of the
BRD complex. There are several
studies out of western Canada documenting that the virus is found
with some consistency in lungs of feeder cattle dying of BRD.
The fact that it is there does not clarify its exact role. It
may be a pneumotropic strain, or it may be acting as an
immuosuppressant. We do see it in some pneumonia cases, but -
at least in range cattle it is not a major factor.
2. It can cause a mild
diarrhea in baby calves, and
exacerbates rotaviral diarrhea.
3. Severe outbreaks of
diarrhea, such as those that were
seen when the disease was first recognized in NY, are seen from time
to time. Such outbreaks are associated with ulcerative lesions
in the gastrointestinal tract, and are usually due to a type 2 BVDV.
We have not recognized this in Wyoming.
4. There are strains of BVDV
that cause a marked reduction in the number of platelets (thrombocytopenia).
Affected calves bleed easily: they have blood diarrhea, nose bleeds
(epistaxis), and blotchy hemorrhages in skin and other tissues.
It can be fatal. We have not seen this in Wyoming.
5. Mucosal disease
is a sporadic disease that affects only PI. Such calves are
infected with a second type of BVDV (invariably a cytopathic strain)
and develop a severe, invariably fatal ulcerative disease of the
gastrointestinal tract. Most but not all PI calves will
develop mucosal disease. A high proportion of PI calves will
develop mucosal disease in their first few weeks in feedlots.
They can also develop mucosal disease as a result of vaccination,
and following spontaneous mutation of NCP to CP. Mucosal
disease is sometimes triggered by vaccinating PI animals with a
modified live viral vaccine.
6. Localized infections
in bulls, BVDV contamination of germplasm
and contamination of bovine fetal
serum. BVDV does some
odd things. One of them is its ability, in a small number of
bulls, survive in testicular tissue for up to 7 months following
acute infection, presumably because the testis is an immunologically
privileged site and it is slow to clear infection. PI bulls
can also look sufficiently good and have semen of adequate quality
that they may be used for AI semen. This is not a common
event, but be aware that semen from AI bulls can contain BVDV and
infect cows. Detecting BVDV in semen, especially when
undiluted, is not an easy task. Semen has several properties
that make it difficult to check it for viral infection, especially
if it is an RNA virus. Semen inhibits viral replication (so
there is not a lot there), destroys cell cultures (so we can't use
cell cultures to grow up the virus), and inhibits reverse
transcriptase (which is used in one of the more sensitive tests we
use to detect viral RNA). BVDV is "sticky" and it will attach
to the surface of fertilized eggs and early embryos. There are
several reports of BVDV being introduced to countries with embryos
intended for implantation. An added complication is that
batches of fetal bovine serum (FBS) can be contaminated by BVDV.
Anywhere between 20 and 49% of FBS batches are contaminated.
Since FBS is used with in vivo derived embryos and in
fertilization, and the benefits of using FBS are lost if it is
irradiated to inactivate BVDV, it is possible to introduce the
virus into embryos.
There are multiple systems to detect
the presence of BVDV in a herd, and I will not inflict all of them
on you - this is a rapidly developing field. We are now close
to a point when it is cost-effective to screen entire herds for PI
animals, and have done so in the recent past. At $3/animal it
is expensive. This cost is coming down as new methods come
There are several tests you need to be aware of. One is based
on examining ear notches (ear notch
test). PI calves have
enormous amounts of virus in all tissues, including skin. The
virus can be detected in skin either by using a specific antibody
and then examining it as on a slide or in an enzyme linked
immunosorbent assay (ELISA). Another is a polymerase chain
test, which allows distinction between the various types of BVDV -
this is important for epidemiological studies, where it is necessary
to find out if all animals were exposed to the same virus. The
gold standard for viral diagnosis is
virus isolation. This is
however slow, and requires good laboratory technique. It can't
be used in suspected PI calves aged between 1 - 4 months.
Material antibodies in the circulation mask the presence of virus.
Pestiviruses resembling BVDV
occur in wildlife, and several of these isolates were made in
We still know little about these isolates and what they do.
Additional work is needed on them (ideally, by inoculating
pregnant cattle to see whether they cause mischief). In
the experience of the WSVL, BVDV is more likely to be introduced
by PI calves than by wildlife. Although not wildlife, the
recent report of persistently infected cria in New World
alpacas), triggering a
remarkable level of concern in that industry. Recent
testing indicates that the occurrence of PIs in alpacas is rare,
and that the source is most likely from other alpaca premises,
rather than from cattle herds.
Recommendations for how to
test and eliminate the disease in spitting beasts have been
There are two other important
pestiviruses that occur in domestic animals. Fortunately,
one of these is eradicated in the US and is regarded as an
exotic disease (classical swine fever). The other occurs
in sheep and, at least in Wyoming, is relatively rare. It
is called Border disease virus, since it was originally
identified on the English-Welch border.
Classical swine fever: This
is currently eliminated in the US but exists elsewhere in
the world, including much of Central and South America, Asia
and Africa. In the past two years it has cropped up in
advanced European counties (e.g., Germany) and in Asia
(e.g., Japan). It is in some senses the foot and mouth
disease of pigs, since it can be transmitted rapidly and
(unlike FMD) some strains are associated with high mortality
rates (up to 90%). And as with FMD, it can be
transmitted by feeding uncooked contaminated garbage
(swill). Vaccines may be available in some areas.
Vaccines can protect animals from clinical disease, but do
not prevent infections. Good vaccination programs can
eventually eliminate the infection in herds.
Border disease in sheep:
This has many of the features of BVD in cattle - it is an
important cause of abortion and perinatal death of lambs in
some parts of the world. It is very closely related to
BVDV and can infect cattle and cause disease.
This has three
components: biosecurity, vaccination and test-and-cull PIs.
It is worth remembering that the Scandinavian countries (Norway,
Sweden, Finland and Denmark) have decided to license no BVDV
vaccines. Instead they focused on biosecurity and test-and-cull.
They have been astonishingly successful. It started in
1993 in Sweden as a voluntary program run by producers. By
2002, 93% and 88% of all dairy and beef herds in Sweden were
a. Biosecurity - keeping
b. Vaccination - keeping
BVD is one of the principal
diseases that producers in Wyoming vaccinate against. More
than 113 USDA-licensed BVDV vaccines are commercially available
- a remarkable number. The vaccines, particularly MLV
products, are moderately effective. THEY DO NOT PROVIDE
COMPLETE PROTECTION AND YOU CAN'T RELY ON VACCINES ALONE.
Most producers are not aware that, although they use the
products to protect the calf in utero, the products don't
have to be tested for their ability to provide fetal protection
- they are mostly tested in adult animals to see if they reduce
the (minimal) clinical effects of BVDV in adult cattle.
Some products (e.g., Pfizer's
have been tested to establish an ability to protect the fetus,
and therefore have a fetal protection (FP) claim.
In vaccination-challenge trials, efficacy of various companies'
products ranges from 25 - 100%. Note that less successful
vaccination-challenge trials performed by or for companies are
unlikely to be published in the scientific literature since it
give competing companies an edge. The 25 - 100% protection
is an upper-end estimate for protection. In one study done
by Pfizer, pregnant cattle previously vaccinated with a type I
BVDV and challenged at 75 days gestation were protected to a
variable degree, depending on whether the challenge (virulent)
strain was type 1 (= 88% protection) or 2 (= 58% protection),
respectively. We've seen large outbreaks of BVDV on common
grazing allotments (for example, an episode seen in
some years ago) where cattle vaccinated against type I BVDV were
then infected with type 2.
A common vaccination strategy is:
Vaccinate heifers with MLV two
months before breeding
Vaccinate cows with MLV two
weeks before breeding
Possibly, boost cows
when pregnant with either a killed product, or a MLV product
to which they have been previously exposed
calves at branding in late spring. This is one time
when it may be appropriate to give a killed product.
There is a good chance that maternal antibody will interfere
and reduce efficacy, so this needs to be repeated by
Vaccinating calves at, or
better still several weeks before, branding time (5 - 7
months of age).
c. Detecting and culling PI
This is best done in Western beef herds an ear notch test.
A small piece of skin is taken from the ear and examined by one
of several methods in a laboratory. Some laboratories
claim that one pattern of staining indicates that PI calves have
a stereotyped distribution of viral antigen in tissue, and that
acutely infected (or vaccinated) calves have little or no viral
antigen in skin. A study done by the Wyoming laboratory by
added a wrinkle to this - a proportion of acutely infected
calves have viral antigen in their skin for months. But
for all intents and purposes, if a calf has viral antigen in
aural skin, it is most likely a PI and should be culled.
If the owner wants to be sure she is culling only PIs, the only
way to truly confirm its status is to retest ~3 weeks after the
first test. If it is a PI, it will remain positive.
If it was acutely infected, or was positive due to recent
vaccination, it will be negative.
Culling in this instance does not mean taking it down to a sale
barn and selling the little time bomb to one of your neighbors -
the ethical thing to do is humanely euthanize the PI calf.
The dam of any PI calf should also be tested. If you
detect a PI in your herd, it may be time to test everyone.
There are strategies to test pooled milk (dairy cows) and serum
(beef cows - not quite as convenient) to establish the status of
herds. This is likely to be a focus of research over the
next few years in order to reduce he costs of testing herds.
by USDA personnel of testing strategies indicate that they are
all over the map - we have some way to go before we agree on the
best, simplest, and cost-effective way to do this. In our
laboratory, we ask that producers submit ear notch samples in 2
ml of phosphate buffered saline, and we test the sample using an
antigen capture ELISA.
There are now several
reports of the use of
pooled blood samples from as many as 100 animals - they are
tested as a pool, and only if a positive is found do the
laboratories test each individual animal to identify the PI.
Several commercial companies, as well as some diagnostic
laboratories, use this approach. In our experience, as
well as that of others, this method misses PIs. There is
no point testing your herd for PIs if the method you use will
not eliminate ALL persistently infected animals.
1. Bovine viral diarrhea
virus is an important and common cause of reproductive loss in
Wyoming beef herds.
2. In addition to
infertility, early embryonic loss, congenital defects and
perinatal loss, infection during a specific gestational window
(90 - 130 days), before the immune system is functional, results
in persistently infected calves that perpetuate infection into
the next generation. This is a classical example of
vertical (one generation to the next) infection.
3. Persistently infected
animals are the main source of infection in herds. Some
will die when superinfected with a cytopathic strain of BVDV,
causing a distinctive clinical syndrome called mucosal disease.
In some ways this is beneficial: they are eliminated from the
4. Most PI calves are born
to non-PI dams. A small proportion of PI calves are born
to PI dams. If you have a PI calf, you MUST test to
dam to make sure she too is not a PI, although the chances of
this are low.
5. BVD is controlled
primarily by 1. good biosecurity; 2. detecting and
eliminating PIs and 3. vaccination.
6. There is a bewildering
range of vaccines for BVD. They are in fact based on a
small number of virus isolates (i.e., vaccines from different
companies may contain the same strain). They are either
inactivated or MLV. As a general rule, MLV are better, but
these should be give to cattle before they are bred. Use a
vaccine that will give some protection against type 1 and type 2
genotypes. Pfizer has a vaccine line that can be given to
pregnant animals, but
COWS MUST HAVE BEEN VACCINATED ONCE
PREVIOUSLY WITH THAT VACCINE BEFORE IT IS SAFE TO GIVE THEM THE
MLV WHEN PREGNANT.
Competing companies are likely to get similar products on the
market (i.e., can be given to pregnant cows) over the next five
7. Even with a good
vaccination program, don't assume BVDV will not enter your herd.
We've seen herds with up to one third of the calf crop being PI,
in spite of excellent vaccination programs. We presume
they were exposed to strains of BVDV that were only distantly
related to the vaccine strain, and therefore the level of
protection was poor. This does not mean the vaccine you
used was "bad" - it is just the nature of a beast that exists in
8. Detecting one animal with
BVDV may mean you have an appreciable problem. On ranches
where we have gone in and tested everyone, and in spite of
owners seeing little overt disease, there have been major
benefits in terms of a healthy calf crop in subsequent years,
PIs were culled. The owners were getting used to a high
incidence of calf scours and pneumonia, and not associating it
with underlying BVD.
8. Some vaccine have a Fetal
Protection claim This is good, since it means that testing
was done to establish the level of protection of calves when
their dams were experimentally vaccinated and then challenged.
But challenge models have limitations. They can't
completely address the range of viral strains in the field.
Such studies can be configured by time of exposure and
dose to ensure the product looks good in promotional literature.
Not all of these studies are published, so it can be hard (or
impossible) without getting the company data to evaluate the
integrity of the challenge model that was used.
8. You can't detect all PI
calves based on physical appearance alone (the coyote-calf
look). There are various methods to detect PIs, such as
virus isolation from blood, or various skin tests.
9. Our recommendation to
eliminate PI animals in the herd is to test all of that year's
calf crop, plus any open cows, plus any bought in cattle.
Do this BEFORE the bulls are put in during the summer -
otherwise you are likely to have another bout of abortions and
perinatal loss the following year. If a calf is positive,
test the dam of that calf to make sure she is not herself a PI.
Most PIs die before adulthood, but a few live long enough to
breed and, if pregnant, will ALWAYS throw a PI calf
There is a excellent
new (2005) textbook devoted to BVD, published recently:
Bovine Viral Diarrhea Virus - Diagnosis, Management and Control.
Eds. SM Goyal and JF
Ridpath - Blackwell Publishing
What would make
you suspect BVD was present in your herd?
persistently infected calves the key to
Why can't you
vaccinate your way out of BVD problem?
laboratory tests that can be used to detect
syndromes associated with BVD.
What is the
standard treatment for a BVDV-persistently
circumstances is it safe to use a MLV on a
What is the recommended test method used by the
WSVL to detect PI calves?
Some owners elect to test for BVD by sampling
calves' ears in the fall at weaning - why is
this not smart?
pestiviral disease, the species in which it
occurs, and what it does.