Transcript Impact of selected Infectious diseases on reproductive performance

Impact of selected Infectious diseases on reproductive
performance in cattle
MSD AH Animal Middle East Symposium
Beirut 2012
Brought to you by Partners in Reproduction Health
Platform
Date
Monika Ptaszynska, DVM, PhD
Global Marketing and Technical Director
Ruminant Reproduction and Uterine Health
Contents
•
Introduction
•
Infections with negative impact on the ovarian functions and higher endocrine regulatory
centres. Example – BVDV infection.
•
Infections causing embryonic and foetal mortality.
•
Unique interaction between infectious factor and the dam’s organism in Neospora
caninum infection.
•
Infections associated with uterine disorders.
•
Infections affecting the quality of semen.
•
Diagnostic decision tree.
•
Safety precautions.
2
Introduction
Infectious causes of reproductive failure in cattle – why so important in
daily veterinary practice….
•
They can have deep and multidirectional negative effect of herd’s reproductive
performance and therefore also on its profitability.
•
Some of them are zoonotic and can represent a risk to the personnel, veterinary
practitioner or even the consumer of products derived from affected animals.
•
Usually these infections find themselves at the very end of the routine diagnostic
process employed in cases of fertility problems in the field and even if abortion took
place only a small percentage of cases is given the correct diagnosis.
•
Nowadays, veterinary practitioners have very good diagnostic methods and
prophylactic measures at their disposal to address the majority of these infections.
3
It is not only about abortions…
Folliculogenesis and ovulation
Indirect effect through impaired
GnRH/LH release
Viruses: BVD, IBR,
Bacteria: H.somni
Generalized infections
accompanied by toxaemia and
fever (e.g. E.Coli mastitis)
Direct effect of the infection
through inflammatory changes
in the ovarian tissues
Viruses: BVD, IBR
Corpus luteum function
Direct negative effect on
placental function and fetal
development
Viruses: BVD, IBR, BTV, Akabane V, probably SBV
Bacteria: Leptospira spp., Campylobacter fetus, A.pyogenes, H.somni,
Ureaplasma spp., Listeria monocytogenes, Chlamydophila spp.,
Coxiella burnetti, Anaplasma marginale, Brucella abortus, Salmonella
spp.,
Fungi: Mucor spp.
Protozoa: Neospora caninun, Trichomonas fetus,Toxoplasma
gondii
4
General timelines for selected infections affecting reproductive
performance in cattle
Neospora caninum
Trichomonas foetus
BTV
Leptospira
interrogans
Fungal inf.
mastitis
BVD
mastitis
BVD IBR
BVD IBR
Follicular phase
Impaired follicular
growth, ovulation
disorders, silent heat
Embryonic phase
(<42d)
Luteal deficiency,
embryonic mortality,
repeat breeding
L.interrogansp
omona
L. interrogans
hardjo
Brucella abortus
IBR
Toxoplasma
gondii,
N.caninum,
BHVAkabane, SBV 4 (?)
C. Fetus
venerealis
Fetal phase (>42d)
Abortions during the 1st half of
pregnancy
Still very limited data for SBV
5
Calving
Abortions in the 2nd half of
pregnancy, often with placental
retention
Stillbirth or
weak
calves
Endo
metrit
is
Infections affecting ovarian functions and higher
endocrine regulatory centers
6
Let’s take a closer look…
Clinical picture at the herd level: low heat intensity, low efficacy of AI, early returns (<25d
post AI.)
Infectious factor
Mechanism
BVDV, IBRV
Multiplication in ovarian tissues and advanced inflammatory changes especially in the ovarian
follicles and corpus luteum
Decreased estradiol secretion
silent heats
Delayed and/or inadequate preovulatory LH surge
errors in AI timing
ovulation delay or failure
Low oocyte/embryo quality and low fertilization rate
Decreased progesterone levels in circulation
Poor embryonic development, EEM
McGowan i wsp., (2002), Fray i wsp., (2002)
Mastitis in periinsemination
period
Inflammatory process and its chemical mediators impair the preovulatory LH surge (Hockett i wsp.,
2000)
Cytokines produced during mastitis can directly impair maturation of the oocytes
7
(Soto i wsp., 2003)
McGowan et al. (2002) – viraemic cows showed decreased or practically absent preovulatory
estradiol peak
No E2 surge!
Dramatyczny
wzrost poziomu
progesteronu
As well as delayed and decreased preovulatory LH surge
8
And what happened with progesterone production in infected cows…
McGowan et al. (2002)
Significantly delayed and
poor increase in
progesterone levels
“Healthy” post ovulatory
progesterone rise
8
7
6
5
4
3
2
1
0
Time from ovulation
24
22
20
18
16
14
12
10
8
6
4
2
BVD+
BVD-
0
Practically no
progesterone rise
Progesterone (ng/ml)
Daily plasma P4 concentrations in cows after intranasal challenge
with non-cytopathogenic BVDV
From Fray et al., 2002
Conclusions: such a low and delayed post-ovulatory progesterone production
will not be adequate to support early embryonic development and pregnancy
recognition
9
Infections causing directly embryonic and fetal
mortality
10
What will happen in the herd…
Clinical picture in the herd: repeat breeding (especially late repeats >25d
post ins.), increased inter-estrus intervals
Infectious factors
Mechanism
BVDV
Negative effect on the fertilization process and early embryonic development
confirmed in vitroo (Booth i wsp., 1998 Bielański i wsp, 2000 Kafi et al., 2002).
Direct negative effect on embryonic development and evidence for embryonic infection
before implantation (Tsuboi i wsp., )
IBRV/BHV-1
Infection of the embryo before implantation and disruption of placentation process
(Miller
i wsp., 1986)
Campylobacter
fetus
Inflammatory process within the oviduct and uterus disrupt the fertilization and impair
the development of the early embryo (Hum 2007)
Tritrichomonas
fetus
Inflammation within the oviduct and uterus may disrupt the embryonic development
and placentation (Rhyan i wsp., 1988; Anderson i wsp., 1996; Singh i wsp., 2005; Midley i wsp., 2009)
N.caninum
It is postulated that the infection can cause late embryonic losses (Innes 2007).
11
What will happen in the herd…
Clinical picture in the herd: abortions, placentitis
Infectious factor
Mechanism/clinical picture
BVDV
Fetal death can practically occur from 45 to 150 day of pregnancy. Direct infection of
the fetus.
IBRV/BHV-1
Fetal death takes place within 24h of viral invasion of the placenta, usually in the
second half of pregnancy. Direct infection of the fetus and placentitis. Abortion occurs
several weeks (20-52 days) after the infection of the dam.
In a naïve, non-vaccinated herd, can lead to abortion storms, with 25 up to even 60%
abortion rate.
BTV
Transplacental infection of the fetus leading to resorption/abortion mainly before 130d of
pregnancy.
Akabane virus
Rarely abortion. Infection in 1st trimester – calves die soon after birth with severe
neurological defects. Infection 2nd trimester – calves born with muscle-skeletal and
nervous system abnormalities
Schmallenberg
virus
No precise mechanism or abortion timing yet established. Abortions suspected to occur
mainly during late pregnancy and considerable time after the infection of the dam. Main
picture – calves born with muscle-skeletal and neurological abnormalities.
Tritrichomonas
fetus
Fetal death takes place mainly between 50 and 70 days of pregnancy. Direct infection
of the fetus and placentitis.
Neospora caninum
Infection during the first trimester almost always leads to fetal death and abortion.
Fetuses are usually aborted between 4 and 6 months of pregnancy. Direct infection of
the fetus.
12
Clinical picture in the herd: abortions, placentitis
Infectious factor
Mechanism/clinical picture
Campylobacter
fetus
Fetal death can take place between 4 and 7 months of pregnancy. Direct infection of the
fetus and placentitis.
Leptospira hardjo
Direct infection of the fetus and placentitis.
Abortions: Serovar hardjo from 4 months of pregnancy (1-3 months post infection),
serovar pomona in the last trimester (1-6 weeks post infection).
Brucella abortus
Direct infection of the fetus and placentitis.
Abortion takes place in 24-72h after the fetal death and usually > 5 months of pregnancy
After abortion placental retention and metritis are common.
Listeria
monocytogenes
Direct infection of the fetus and placentitis.
Abortion during the last trimester often followed by placental retention and
metritis/endometritis.
H.somni
Direct infection of the fetus and placentitis.
Abortions usually in late pregnancy.
Coxiella burnetti (Q
fever),
Chlamydophila
abortus
Sporadic abortions, mainly in late pregnancy (6-8 months) often followed by metritis and
endometritis. Usually associated with close proximity to herds of small ruminants.
Salmonella Dublin
Abortions usually take place in the second half of pregnancy and are followed by
placental retention.
13
Unique interaction between infectious factor and the dam’s organism in
N.caninum infection
Important role of the specific immune situation of the pregnant cows (immunotolerance of fetal antigens)
and activation of the immune response in face of the parasite re-activation (Innes i wsp., 2007).
In order to maintain pregnancy (semi-allogenic
transplant) the maternal organism gives
preference to regulatory cytokines: IL-10, IL-4,
TGFb, having an opposite effect to inflammatory
type cytokines (INT)
Immunosuppressive
effect of
progesterone????
Infection with N. caninum usually induces
cellular immune response with important
participation of lymphocytes T and INT 
It is thought that the natural immuno-modulation that guarantees
pregnancy maintenance may impair the ability of the cows to
mobilize the cellular immune response adequate for elimination of
the parasite.
It is also postulated that apart from the direct effect of the parasite
on the fetal development, the immune response activated within the
placenta may have a fetotoxic effect and lead to abortion.
14
Infections typically accompanied by endometritis
Infectious factor
Mechanism/clinical picture
Brucella abortus
Endometritis and salpingitis leading to decreased fertility and infertility.
Listeria
monocytogenes
After abortion: placental retention and metritis/endometritris.
Campylobacter
fetus
Endometritis, moderate cervicitis and salpingitis.
H. somni
Nonspecific endometritis of variable intensity.
Tritrichomonas
fetus
Endometritis, moderate cervicitis and salpingitis.
BHV-4
In the US cases of purulent, ulcerative endometritis associated with BHV-4
infection were described in cows in the early post partum period (Wellemans i
wsp.,1984; Frazier i wsp., 2001,Frazier i wsp., 2002; Gur 2010)
15
Infections affecting the semen quality
Infectious factor
Mechanizm
Decreased semen
quality
Shedding with semen
Brucella abortus
Inflammation of the testicles,
seminal vesicles and epidydimis
Yes, acute & chronic
phase
Yes, directly
Camp. fetus
Usually asymptomatic
Usually Not
Yes, indirectly
Leptospira hardjo
Replication in the testicles and
seminal vesicles
Yes, acute & chronic
phase
Yes, directly
H. somni
Replication in the testicles and
seminal vesicles
Yes, acute & chronic
phase
Yes, directly
Wirus IBR
Replication in the testicles and
seminal vesicles.
Balanoposthitis
Possible in acute
phase, usually Not in
chronic phase.
Yes (periodical
activation due to
immunosuppression)
throughout the lifetime
Wirus BVD
Replication in the testicles and
seminal vesicles
Possible in acute
phase, usually Not in PI
individuals
Yes in the acute phase,
PI individuals in large
quantities, permanently
BTV
Replication in the testicles and
seminal vesicles
Possible in acute phase
Yes in the acute phase
Trich. fetus
Usually asymptomatic
Usually Not
Yes, indirectly
N. caninum
Not defined
Usually Not
Probably limited
16
Orientation diagnostic decision tree
Low reproductive
results
Decreased fertility
Abortions in 1st trimester
AI only
Silent heats
Low AI efficacy
Early repeats
AI only
BVD
IBRV
Mastitis
BVDV
BTV
L.hardjo
N.caninum
NM & AI, NM only
♂♀
IBRV
BVD
Trich. Fetus
Camp. Fetus
Mastitis
Abortions in 2nd half of pregnancy
AI only
IBRV
B.abortus
L.hardjo
L.pomona
L.monocytogenes
N.caninum
SBV
C.burnetti
Ch.abortus
S.Dublin
H.somni
Late repeats
Increased heat intervals
AI only
BVD
IBRV
NM & AI, NM only
♂♀
BVDV
BTV
L.hardjo
Camp. Fetus
Trich. Fetus
N.caninum
NM & AI, NM only
♂♀
IBRV
BVD
Trich. Fetus
Camp. Fetus
17
NM & AI, NM only
IBRV
B.abortus
Camp. Fetus
L.hardjo
L.pomona
L.monocytogenes
N.caninum
SBV
C.burnetti
Ch.abortus
S.Dublin
H.somni
What are our possibilities for diagnosis and control in
some of the infections?
Infectious factor
Diagnostics
Eradication/prophylactics
Brucella abortus
Cow: ELISA, PCR
Fetus: isolation, PCR
Monitoring & elimination of positive individuals
In some countries vaccination (RB51)
Camp. fetus
Cow, bull: isolation, IFAT, ELISA, PCR
fetus: isolation, PCR
Monitoring & elimination of positive individuals
Strict control of bulls
In some countries vaccination
Shift to AI
BVD
Cow: ELISA,
Fetus: isolation, IFAT, PCR
Monitoring & elimination of PI individuals
Vaccinations (Important: with products that afford
protection against transplacental infection)
IBR
Cow: ELISA,
Fetus: isolation, IFAT, PCR
Monitoring & elimination of positive individuals
Vaccination & eradication programs (based on
marker vaccines)
BTV
Cow: ELISA,
Fetus: isolation, IFAT, PCR
Vaccination
Control of the vectors.
Trich. fetus
Cow, bull: isolation, PCR
Fetus: isolation, PCR
Monitoring & elimination of positive individuals,
Strict control of bulls
In some countries vaccination (♀)
Shift to AI
SBV
Fetus: PCR detecting viral antigens only
available at present.
No measures available yet. Control of vectors
available.
18
On the safety…
•
Due to the zoonotic potential, care should always be taken when handling
the abortion material to ensure safety of the veterinary surgeon, their
assistants and bystanders.
•
Adequate instruction should be given to the owners and personnel in
contact with aborting animals to ensure their safety.
•
If an infectious cause of the abortion/stillbirth is suspected the affected
animal should be isolated, the place where abortion took place cleaned and
disinfected and the abortion material safely disposed after the adequate
samples have been collected.
•
In particular pregnant women and women of child-bearing age should avoid
contact with aborted material.
19
Thank you very much for your kind attention
Questions…
20