Infectious Causes of Infertility.pptx

INFECTIOUS CAUSES OF INFERTILITY JUSTIN T. HAYNA, DVM, DACT VCS 80801 EQUINE MEDICINE LECTURE TOPICS • Contagious Equine Metritis • Mare Reproductive Loss Syndrome • Equine Viral Arteritis • Equine Herpes Virus LECTURE OBJECTIVES • Explain a testing and treatment plan to detect the diseases disc...

INFECTIOUS CAUSES OF INFERTILITY JUSTIN T. HAYNA, DVM, DACT VCS 80801 EQUINE MEDICINE LECTURE TOPICS • Contagious Equine Metritis • Mare Reproductive Loss Syndrome • Equine Viral Arteritis • Equine Herpes Virus LECTURE OBJECTIVES • Explain a testing and treatment plan to detect the diseases discussed today • List diagnostic techniques to diagnosis equine abortigenic diseases • Understand the pathophysiology of why these diseases cause abortions or infertility • Discuss control measures to survey, reduce or eradicate these diseases CONTAGIOUS EQUINE METRITIS • aka CEM • Federally regulated venereal disease of horses • Reportable • Considered a Foreign Animal Disease • Massive economic losses • McKinnon & Voss Equine Reproduction 2nd Ed. Pg 2399-2407 CEM • Causative Agent: Taylorela equigenitalis • Gram –, cocco-bacillus • Fastidious • Two Biotypes (Streptomycin resistant v Non-resistant) • Not very durable • High fomite transmission CEM: CLINICAL SIGNS • Stallion • NONE, Non-infected carriers • Mare • • • • Mucopurulent vaginal discharge shortly after live cover matings Endometritis, cervicitis, vaginitis Early return to estrus, why? These issues cause an environment that is hostile to embryos thus infertility • Incubation Period • 3-13 days post breeding CEM: TRANSMISSION • Direct venereal contact • Mare to foal?? • Fomites • Phantom, AV’s, Wash buckets • Stallion to stallion • Immune Response • Mares commonly have a humoral immune response • Mare will seroconvert • Subsequent breeding to infected stallions have greatly diminished inflammatory response CEM: DIAGNOSIS • Culture • Fastidious nature of organism requires strict conditions • Charcoal Aimes culturettes, Chocolate-Blood agar plates • Contact USDA if you plan to screen stallions, Aimes IA Lab will send you proper materials • Test Breeding • Suspect stallions are bred to confirmed non-infected, serologically negative mares • PCR • May be more sensitive CEM • Culture Sites • Stallion • Urethral fossa, urethral sinus, urethra, penis, prepuce • Mare • Endometrium, cervix, clitoral sinus, clitoral fossa CEM • Treatment • Mare • Clean and lavage clitoris and clitoral fossa/sinuses • Clitorosinusectomy? • Stallion • Clean penis, wash with 4% chlorhexidine gluconate • Liberally apply nitrofurazone or silver sulfadiazine ointment MARE REPRODUCTIVE LOSS SYNDROME • aka MRLS • Defined in KY and OH in 2001 • Thoroughbred broodmare farms • $500 Million loss • Similar disease reported in Australia • Equine Amnionitis and Fetal Loss (EAFL) MRLS • Clinical Signs • • • • • • Non-viable fetus Hyperechoic allantoic/amniotic fluid Vulvar discharge +/Fetal membrane/fetal expulsion Late term abortion, 300+ days Amnionitis, Funisitis • Roughened, gray-yellow discolored umbilicus • Early Fetal Loss (EFL) • Detected after 37 days • Usually between 55-75 days • Late Fetal Loss (LFL) • 300 days or more • Fibrinous pericarditis/Rtsided failure • Endophthalmitis MRLS • Cause • • • • ????? Eastern tent caterpillar Black cherry trees There was a massive explosion of these caterpillars that year MRLS • Horses were ingesting either caterpillars, caterpillar feces, or discharge • Studies found that caterpillar exoskeleton or cuticle was abortigenic • But, no evidence to provide how the clinical signs were created • No direction at determining compound that caused the clinical signs • Septic Penetrating Setal Hypothesis • Ingestion of barbed setal fragments of ETC associated with bacterial “hitch-hikers” followed by hematogenous spread of these bacteria which give rise to the clinical signs of MRLS • Streptococcus and Actinobacillus species were culture from fetal aborted MRLS: TREATMENT • Reproductive Cases • EFL → Nothing worked • LFL → Supportive, poor prognosis • Pericarditis • Pericardiocentesis, thoracocentesis, antibiotics, supportive care • Ophthalmology • Nope EQUINE HERPES VIRUS • EHV 1 • EHV 3 • EHV 4 EQUINE COITAL EXANTHEMA EHV-3 • Transmission • Venereal • AI, Fomites • Clinical Signs • 2mm red, angry, circular, nodule/ulcerative lesions • Vulva, perineum, clitoral area, penis • Commonly secondarily infected (Strept. Zoo) • Discharge • Low libido/interest/refusal EQUINE COITAL EXANTHEMA EHV-3 • Diagnosis • Clinical signs, electron microscopy • Treatment • • • • • Sexual rest Lesions generally heal in 3 weeks (2-5) Supportive care Disinfect equipment, use disposable items (Fomites) No vaccine EHV-3 EHV-1 & 4 • 1 is the greater issue for abortion and neonatal mortality • Although EHV 4 may be a greater cause of febrile respiratory disease • Neonates, <2yr olds • EHV 1 also causes myeloencephalopathy • Multisystemic vasculitis • Latency/Carrier states • McKinnon & Voss, 2nd Ed. Pg 2376-2390 EHV-1(4) TRANMISSION • Almost 100% • Respiratory route is primary • Ingestion • Transplacental • Inhalation of infected material (direct/indirect) • Shedding 7-15 days • Incubation 1week to several months • Abortions usually within 15-30 days • Aborted tissues are highly contaminated with virus • Limited information on spread of virus via semen or embryo transfer EHV-1(4) CLINICAL SIGNS: ABORTION • Without systemic respiratory signs of mare • “Abortion Storms” 75% • Maidens • 5 months gestation to term • 7-10 months of gestation most common • Few issues <5 months due to • placental resistances to EHV and prostaglandin production • lack complete morphologic placenta • Very late term infection → abortion/parturition • High respiratory morbidity/mortality • Foals EHV-1(4) PATHOGENESIS: PLACENTAL INFECTION • Infects the uterine endothelium → endometrial vasculitis • Vasculitis of endometrium → microcotyledonary infarction and thrombosis • Tissue disruption/edema → premature placental separation • Damage can then extend to chorioallantois • Transplacental migration via infected leukocytes • Fetal infection occurs over time/severity of placental infection • Less severe placental infection will allow time for fetal infection EHV-1(4) DIAGNOSIS • Clinical Signs • Late gestation abortion • Premature placental separation • “Red Bag” • Heavy, edematous placentas • Diffuse gross placental lesions • Weak, sick, quickly dying foals • Viral Isolation, PCR/Histopathology • Chorioallantois • Fetal lung, liver, spleen • Frozen v Formalin • CALL YOUR DIAGNOSTIC LAB EHV-1(4) TREATMENT/CONTROL • Supportive care • Isolation of new arrivals • Separation of pregnant broodmares • Aborted tissues are highly infective • Vaccination • 5, 7, 9 months gestation • Protective immunity lasts 3 months • • Wild-type and immunization Cell-mediated immunity is very important EHV1 (4) CARRIER STATE • Natural reservoir is the carrier animal • T lymphocytes and trigeminal ganglia • CD4 and CD8 T-Lymphocytes • Creates the cell-associated viremia • Reactivation • Stress, transport, corticosteroids ect ect Fig 248.1 McKinnon and T. Flury with Carrasca Z EQUINE VIRAL ARTERITIS • aka EVA • Worldwide distribution • Major recent outbreaks in US • Respiratory and Abortigenic • Standardbreds • McKinnon & Voss, 2nd Ed. Pg 2391-2398 EVA • Positive sense RNA virus • Enveloped • Single strand • Generally easily inactivated (heat, chemical, dehydration) • Very stable at cold, freezing temperatures • Related to Porcine Reproductive and Respiratory Syndrome Virus EVA TRANSMISSION • Direct contact with infected tissues, fluids, animals and fomites • Respiratory route • Major form of infection for male and female • Venereal spread • Stallion to Mare • Semen • Transplacental • Mare to Fetus(Foal) EVA CLINICAL SIGNS • Incubation • 2-13 days, respiratory route • 6-8 days for venereal transmission • Respiratory • They get really sick (fever, anorexia, lethargy, leukopenia) • Primary source virus to other horses • Source of abortion in late gestational mares EVA CLINICAL SIGNS • Reproductive • Dependent edema of mammary gland, prepuce and scrotum • Transient infertility in both genders • Abortion 3-10 months gestation EVA PATHOGENESIS • “Similar to EHV” • Virus infects macrophages and vascular myocytes/endothelium → Vasculitis • Viral replication activates increased transcription of pro-inflammatory mediators • Maximum vascular injury by ~10 days EVA ABORTION PATHOGENESIS • Abortigenic pathogenesis is undetermined • Vasculitis is minimal or not seen • Fetal death appears to occur prior to parturition/abortion • Differs from EHV • Sequalae to respiratory exposure in late gestation • Not harboring virus at conception EVA MARE ISSUES • Respiratory transmission during pregnancy is what leads to abortion • Transplacental migration of the virus occurs and likely kills the fetus • There is no evidence to suggest a mare bred with infected semen or infected embryo transfer leads to late gestation abortion • Venereal transmission usually causes transient infertility • Creates endometritis and possible respiratory signs • Naïve mares readily seroconvert and do not appear to suffer from future issues • These mares are strong sources of infection to pregnant mares EVA STALLION ISSUES • Respiratory infection causes fever and local inflammation associated with vasculitis → edema and swelling • Increased testicular temperatures impair spermatogenesis at the primary spermatocyte and spermatid stage • Poor semen quality can be seen 10 to 75 days after insult • Carrier State Establishment • The virus has a predilection for tissues high in androgens (Testosterone, 5-DHT) EVA TREATMENT, TESTING AND CONTROL • Treatment is geared at supportive care. Disease is rarely fatal in adults • Carrier stallions are almost impossible to clear of virus • Few stallions naturally clear virus • GnRH vaccination/antagonists have shown promise in clearing virus • • • How would this work? Issue is that no studies have been done on long term affects Products are not in US EVA TESTING • Respiratory cases • Nasopharyngeal Swabs and RT-PCR • Abortions • Viral isolation and histology • Fetal lung, liver and placenta EVA SCREENING • Non-sick animals can be screened to see if they have been exposed • Titers do not differentiate between vaccinated and unvaccinated animals • Antibody titer testing can be performed on females and males • Seropositive animals can be highly resistant to the disease • Except for stallions/colts, seropositive carriers can be the norm EVA TESTING AND VACCINATION • Colts are tested and immediately vaccinated • Negative titer • not exposed • very likely not a carrier or infected very recently • Positive titer • Exposed • Semen analysis, RT-PCR to determine if shedder of virus EVA VACCINE • Single dose, powder/dilutent • Single dose/yr, 4-8 week booster not needed • Long shelf life • EXPENSIVE • Some states have restrictions on vaccination • Contact your state veterinarian or Dept. of Agriculture EVA ERADICATION • Carrier state is a primary reservoir and source of genetic drift in horses • EAV harbors in high androgen tissues • Vaccination of all colts prior to puberty would likely eliminate the disease • Document when you vaccinate and titer. Some countries will not accept horses or semen from a horse with a positive titer OTHER CAUSES • Lepto Pomona and grippotyphosa • Potomac Horse Fever • Rhodoccocus equi • Salmonela abortus equi QUESTIONS? S. Crawford with Mario QUIZ QUESTION #1 • You examine a maiden mare for the first time that has with a normal TPR, a mildly hyperechoic fluid filled uterus and purulent vulvar drainage. You diagnose? • A: Metritis • B: Infectious Endometritis • C: Post-Breeding Endometritis • D: Persistent Post-Breeding Endometritis QUIZ #2 • Mares with endometritis commonly benefit from being in estrus. How can we assist that mares are in estrus? • A: Administer progestins • B: Administer PGF2-α • C: Administer antibiotics • D: Administer deslorelin QUIZ #3 • After breeding a mare, you check her the next day and confirm ovulation and see the mare’s uterus is full of fluid. You diagnose • A: Post-breeding endometritis • B: Anovulation • C: Pyometra • D: Metritis