Date 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 Monika Ptaszynska, DVM, PhD Global Marketing and Technical Director Ruminant Reproduction and Uterine Health

2 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.

3 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.

4 It is not only about abortions… Folliculogenesis and ovulation Corpus luteum function 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 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

5 General timelines for selected infections affecting reproductive performance in cattle Follicular phase Embryonic phase (<42d) Fetal phase (>42d)Calving BVD IBR mastitis Brucella abortus C. Fetus venerealis Leptospira interrogans L. interrogans hardjo L.interrogansp omona Fungal inf. BVD IBR BTV Trichomonas foetus Neospora caninum Toxoplasma gondii, N.caninum, Akabane, SBV Impaired follicular growth, ovulation disorders, silent heat Luteal deficiency, embryonic mortality, repeat breeding Abortions during the 1 st half of pregnancy Abortions in the 2 nd half of pregnancy, often with placental retention Stillbirth or weak calves BHV- 4 (?) Endo metrit is Still very limited data for SBV

6 Infections affecting ovarian functions and higher endocrine regulatory centers

7 Let’s take a closer look… Infectious factorMechanism BVDV, IBRV Multiplication in ovarian tissues and advanced inflammatory changes especially in the ovarian follicles and corpus luteum Decreased estradiol secretion silent heats errors in AI timing Delayed and/or inadequate preovulatory LH surge 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 peri- insemination 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 (Soto i wsp., 2003) Clinical picture at the herd level: low heat intensity, low efficacy of AI, early returns (<25d post AI.)

8 McGowan et al. (2002) – viraemic cows showed decreased or practically absent preovulatory estradiol peak As well as delayed and decreased preovulatory LH surge No E2 surge! Dramatyczny wzrost poziomu progesteronu

9 And what happened with progesterone production in infected cows… “Healthy” post ovulatory progesterone rise Significantly delayed and poor increase in progesterone levels Practically no progesterone rise McGowan et al. (2002) 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

10 Infections causing directly embryonic and fetal mortality

11 What will happen in the herd… Infectious factorsMechanism BVDVNegative 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-1Infection 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.caninumIt is postulated that the infection can cause late embryonic losses (Innes 2007). Clinical picture in the herd: repeat breeding (especially late repeats >25d post ins.), increased inter-estrus intervals

12 What will happen in the herd… Infectious factorMechanism/clinical picture BVDVFetal death can practically occur from 45 to 150 day of pregnancy. Direct infection of the fetus. IBRV/BHV-1Fetal 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. BTVTransplacental infection of the fetus leading to resorption/abortion mainly before 130d of pregnancy. Akabane virusRarely abortion. Infection in 1 st trimester – calves die soon after birth with severe neurological defects. Infection 2 nd 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 caninumInfection 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. Clinical picture in the herd: abortions, placentitis

13 Infectious factorMechanism/clinical picture Campylobacter fetus Fetal death can take place between 4 and 7 months of pregnancy. Direct infection of the fetus and placentitis. Leptospira hardjoDirect 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 abortusDirect 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.somniDirect 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 DublinAbortions usually take place in the second half of pregnancy and are followed by placental retention. Clinical picture in the herd: abortions, placentitis

14 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, TGF  having an opposite effect to inflammatory type cytokines  (INT  ) 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. Immunosuppressive effect of progesterone????

15 Infections typically accompanied by endometritis Infectious factorMechanism/clinical picture Brucella abortusEndometritis 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. somniNonspecific endometritis of variable intensity. Tritrichomonas fetus Endometritis, moderate cervicitis and salpingitis. BHV-4In 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)

16 Infections affecting the semen quality Infectious factorMechanizmDecreased semen quality Shedding with semen Brucella abortusInflammation of the testicles, seminal vesicles and epidydimis Yes, acute & chronic phase Yes, directly Camp. fetusUsually asymptomaticUsually NotYes, indirectly Leptospira hardjoReplication in the testicles and seminal vesicles Yes, acute & chronic phase Yes, directly H. somniReplication in the testicles and seminal vesicles Yes, acute & chronic phase Yes, directly Wirus IBRReplication 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 BVDReplication 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 BTVReplication in the testicles and seminal vesicles Possible in acute phaseYes in the acute phase Trich. fetusUsually asymptomaticUsually NotYes, indirectly N. caninumNot definedUsually NotProbably limited

17 Orientation diagnostic decision tree

18 What are our possibilities for diagnosis and control in some of the infections? Infectious factorDiagnosticsEradication/prophylactics Brucella abortusCow: ELISA, PCR Fetus: isolation, PCR Monitoring & elimination of positive individuals In some countries vaccination (RB51) Camp. fetusCow, bull: isolation, IFAT, ELISA, PCR fetus: isolation, PCR Monitoring & elimination of positive individuals Strict control of bulls In some countries vaccination Shift to AI BVDCow: ELISA, Fetus: isolation, IFAT, PCR Monitoring & elimination of PI individuals Vaccinations (Important: with products that afford protection against transplacental infection) IBRCow: ELISA, Fetus: isolation, IFAT, PCR Monitoring & elimination of positive individuals Vaccination & eradication programs (based on marker vaccines) BTVCow: ELISA, Fetus: isolation, IFAT, PCR Vaccination Control of the vectors. Trich. fetusCow, bull: isolation, PCR Fetus: isolation, PCR Monitoring & elimination of positive individuals, Strict control of bulls In some countries vaccination (♀) Shift to AI SBVFetus: PCR detecting viral antigens only available at present. No measures available yet. Control of vectors available.

19 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.

20 Thank you very much for your kind attention Questions…