Equine Health Management September 21, 2011 Equine Vaccinations Equine Health Management September 21, 2011

Controlling Infectious Disease What is an infectious disease? Contagious disease Virus, bacteria, parasite, fungi and protozoa When is infectious disease a problem? When a horse or group of horses experience a challenge from an infectious agent at a dose sufficient to overcome resistance Where do horses acquire resistance? Previous natural exposure or vaccination define contagious Transmission of an infectious disease may occur through one or more pathways including physical contact with infected individuals. These infecting agents may also be transmitted through liquids, food, body fluids, contaminated objects, airborne inhalation, or through vector-borne spread (i.e., ticks, mosquitoes, etc.)

Protecting Against Infectious Disease Three goals when it comes to protecting your horses against infectious disease: Reduce exposure in the environment Minimize factors that decrease resistance Enhance resistance through the use of vaccines** What causes increased incidence? Management Animal Environment **vaccination alone will not prevent disease!! You must also have good management to reduce risk of exposure. Management includes: stocking densities, movement of horses off/on farm Animal: age, breed, sex, use, previous exposure Environment: climate, geography, layout of facility

Vaccinations Vaccination minimizes risk but does not prevent disease Follow instructions re: primary series (vaccines and boosters) before likely exposure Not all horses respond the same or are protected for the same length of time All horses in a herd should be vaccinated on the same schedule when possible to optimize herd immunity How do you know when to administer to prevent disease prior to exposure?? Know how vaccines work! They are not instantaneous protection!

Tetanus WNV EEE/WEE/VEE EHV1&4 Influenza Rabies Strangles Potomac Horse Fever Botulism Rotavirus Killed or inactivated Modified live or attenuated Genetically engineered Mono or multi-valent IM / IN There is no such thing as a “standard” vaccination protocol – it all depends on the type of facility and animals you are dealing with! Choice of a variety of different types of vaccines directed against a variety of antigens; determine the age of susceptibility for various diseases

Types of Immunity Humoral Immunity: Cellular Immunity: B lymphocytes and plasma cells produce antibodies to foreign agents and stimulate T lymphocytes to attack them Cellular Immunity: Immune response that involves enhanced activity by phagocytic cells and does not imply lymphocyte involvement. Mucosal Immunity: Resistance to infection across the mucous membranes. Dependent on immune cells and antibodies present in the lining of the urogenital tract, gastrointestinal tract and other parts of the body exposed to the outside world.

Contagious: Horse to Horse Spread horse to horse Influenza virus: respiratory secretions, equipment Herpes virus: respiratory secretions, equipment, aborting mares shed via uterine fluids, latent infections, asymptomatic shedders Strangles: nasal discharge, draining abscesses, equipment, water troughs, environment , asymptomatic shedders Rotavirus: manure, fomites Salmonella: manure, fomites (people, stall cleaning equipment) A fomite is any inanimate object or substance capable of carrying infectious organisms (such as germs or parasites) and hence transferring them from one individual to another With this kind of disease, a humoral response would be ideal (protects the entry routes – i.e., throat, nasal passage, etc.)

Population Dynamics Closed herd Open herd Only resident horses Uniform vaccination/ deworming protocols Open herd Outside horses Recipient or Nurse mares Performance/ show horses Young horses Rhodococcus equi and Strangles are most prevalent in open herds

Vaccinations Core Vaccines Regional Endemic Breed (WmB) Tetanus, EEE, WEE, WNV, EHV1&4, Influenza, Rabies Regional Botulism: Mid-Atlantic area PHF: areas of fresh water Endemic Strangles Rotavirus Breed (WmB) EVA WmB = warmblood

Inactivated (Killed) Vaccine Organisms not replicating Adjuvants added to boost immune response Advantages: Safety, stability Disadvantages: Slower onset of protection, shorter duration of immunity Reactions associated with adjuvants Slower onset  protection generally is not achieved until 2 to 3 weeks after completion of the primary series or 1 or more weeks after administration of a booster dose. *Work better when given as a 3-dose series than as a 2-dose series! *3 to 4 week interval between the first and second doses of vaccine followed by a longer interval of 3 to 5 months between the second and third doses  optimize priming of the immune system and protection.

Adjuvants Immunomodulation Interaction between adjuvants? Stimulate or slow the immune response Increase response to vaccine No antigenic effect itself Interaction between adjuvants? Different companies use different adjuvants Local reaction to adjuvants Wide variety Aluminum salts. Saponins, Oil emulsions, Liposomes an adjuvant is an agent that may stimulate the immune system and increase the response to a vaccine, without having any specific antigenic effect in itself. The word “adjuvant” comes from the Latin word adjuvare, meaning to help or aid. "An immunologic adjuvant is defined as any substance that acts to accelerate, prolong, or enhance antigen-specific immune responses when used in combination with specific vaccine antigens."

Attenuated (MLV) Vaccine Attenuated: organism is modified so it is non-pathogenic but still causes immune response - replicates within the host Advantages: Rapid onset of immunity Longer duration of immunity No adjuvant Disadvantages: Potential for inactivation Reversion to virulence Requires reconstitution Examples: Flu-AVERT® intranasal influenza vaccine Pinnacle® intranasal Strangles vaccine Rhinomune® intramuscular EHV-1 vaccine

Genetically Engineered Vaccines: A new breed of vaccines! Category I: Subunit Category II: Gene deletion Category III: Clone genes into vector (bacteria or virus); vector transports genes & expresses the antigens when administered to host Recombitek®: Canary pox virus vector used Advantages: Safety Antigenic specificity Longer duration

Toxoids vs. Antitoxins Toxoid: Deactivated toxin - vaccine Tetanus toxoid Antitoxin: preformed antibody - treatment Tetanus antitoxin Botulinum antitoxin R. equi hyperimmune serum Rapid, but short-lived protection

Immunization Failures Host: Compromised host; steroids? Maternal antibody interference Vaccine: Inappropriate strain (PHF) Improper storage & handling; outdated Bell curve: some horses respond better than others! Human Error: Misuse Too frequent administration: wait a minimum of 2 wks between doses or between different vaccines Never vaccinate a sick horse or one on steroids (i.e., prednisone) OK to give multiple vaccines in one day, but don’t come back in 5 days and give another; wait at least 2 weeks!

Foal Vaccination Program: Dam’s vaccination status Colostrum quality/FPT Risk of diseases Regional Endemic to farm Husbandry practices Vaccine used/age at initial vaccination/ number of doses Foal’s immune response FPT = Failure of Passive Transfer

Foal Immunity Passive Immunity Maternally derived antibodies in colostrum Temporary protection Immunity gap / window of susceptibility: the period during which MDA have fallen below protective levels but still interfere with the foal’s response to immunization Varies with different antigens (diseases) and different vaccines

Impact of MDA on Immune Function in the Foal Maternally derived antibodies (MDA) provide passive protection while suppressing the foal’s ability to synthesize its own antibodies Rate of decline of MDA varies for both individuals and antigens [MDA] fall below protective levels for most antigens by 3 months of age, but remaining antibody levels may still block the foal’s response to vaccination

Maternal Antibody Interference EEE / WEE Tetanus EHV-1&4 Influenza Rabies Rotavirus

Misdirected Immune Response Inactivated vaccines administered to young foals (< 6mos) stimulate mostly IgG(T) and little to no IgGb which is the most immunoprotective antibody Immunosuppression by high levels of colostral IgGb Foal [IgGb] lagged behind adult levels for > 6mos Recommend delaying primary vaccination with inactivated vaccines until foals are at least 6 mos old Foal production of IgGb not detected until at least 63 d of age

Diseases: What protects? Humoral antibody EEE / WEE / WNV Tetanus Rabies Botulism Combination EHV1&4: Humoral, cellular, mucosal Rotavirus: IgA, humoral Influenza: Humoral, mucosal Streptococcus equi: Humoral, mucosal

EHV-1: What we know… EHV-1 becomes latent in ~80% of horses infected Latency established in trigeminal ganglion & lymphocytes Natural immunity is short lived (3 – 6 months) but may increase after repeated exposure In broodmares, immunity against abortion appears to be more durable following natural infection. Infection is spread by direct contact between horses and infected equipment

Abortion of virus (+) fetus or dying foal EHV-1 Maternal endothelial cell infection Fetal Infection Placenta Fetal death Endometrial vasculitis, thrombosis, ischemia Abortion of virus (+) fetus or dying foal “Red Bag” “ Abortion of virus (-) fetus

EHV: Vaccines Killed Vaccines: Respiratory claim Prestige®: IM Calvenza®: IM / IN Innovator®: IM Modified Live: Respiratory claim Rhinomune®: IM Killed Vaccines : Abortion claim; approved for pregnant mares Prodigy®: IM Pneumabort K® : IM Prodigy and Pneumabort are for EHV-1 ONLY;

Herpes vaccines Should I use a vaccine with EHV-1 and 4 or just EHV-1? EHV-4 causes the majority of herpes respiratory disease in young horses EHV-1 causes abortion and CNS disease as well When should I use a EHV-1 only vaccines? During pregnancy: months 5, 7, 9 To reduce the risk of neurological EHV-1 disease? There is cross protection between EHV-1 and 4 NO vaccine has a label claim to prevent the neurological form of EHV-1!! Use of EHV-1 only vaccine may improve immunity, but not necessarily so!

Influenza Not a clinical problem in foals No longer necessary to have Influenza A type 1 in vaccines; should have clinically relevant A/equine 2 subtype in current vaccines MLV Intranasal provides rapid onset of immunity (within 7 days) & longer duration of immunity Use IM influenza vaccines to booster dam’s immunity Generally only a problem in yearlings  about 3 years old (sometimes older); not usually a problem in adult horses

Modified Live Influenza Vaccine Stimulates local immunity Rapid onset of immunity within 7 days Safe in stressed animals (e.g., transportation, weaning) Single dose for primary immunization Begin vaccination at 11 months; booster every 6 months

Strangles: Immunity & Vaccination Immunity following recovery from disease Dependent upon inoculum dose, virulence, and pre-existing immunity Solid immunity for 5 yrs or longer in 75% of animals Foals born to recovered mares Colostrum contains IgG & IgA; milk contains IgA Foals generally protected until weaned Foals born to vaccinated mares Varies depending upon mare’s response Variable protection for 3-6 months Only vaccinate if at risk or unknown farm status (i.e. endemic problems)

Strangles: Vaccination Vaccines SeM protein extract vaccines (Bacterins) Intramuscular Reactive: use hindlimb Attenuated live vaccine Intranasal Accidental contamination of other injection sites When you use the IM vaccine always use hindquarters and then get horse out and moving. Don’t give ANY other vaccine at the same time as the intranasal (see photo) – can cause a massive pus-filled nasty mess.

Complications Purpura Hemorrhagica Do not over-vaccinate! Necrotizing vasculitis – immune complex Edema, petechial & ecchymotic hemmorrhage May develop after vaccination or exposure to clinical disease High titers predispose Do not over-vaccinate! Vasculitis = inflammation of the blood vessels Petechial = is a small (1-2mm) red or purple spot on the body, caused by a minor hemorrhage (broken capillary blood vessels) Ecchymotic = A small haemorrhagic spot, larger than a petechia, in the skin or mucous membrane forming a nonelevated, rounded or irregular, blue or purplish patch Titer = number of antibodies present (concentration)

Strangles Protection on Hi-Risk Farms Yearlings and Performance horses: IN every 6 mos; IM every 4-6 mos Broodmares: IM booster last 4-6 wk of pregnancy Foals: IN begin at 6 mos with 2 doses @ 3wk intervals IM begin at 4-6 mos with 3-dose series Avoid vaccinating horses with high serum titers Horses with very high titers due to natural infection or vaccination are at increased risk of purpura and other immune mediated complications

TETANUS (Lock-jaw) Not contagious; organism lives in the environment in low oxygen conditions C. tetani enters via puncture wounds (especially in the foot), lacerations, surgical incisions (e.g. castrations), umbilicus of foals Horses are the most susceptible species Very high mortality (80%) - Clostridium tetani bacteria is a normal contaminant of the horses intestinal tract and feces.

Tetanus All horses should be vaccinated for tetanus Vaccine is safe Good immunity; at least 1 year, probably longer Disease can be fatal and is expensive to treat All horses should be vaccinated for tetanus Check vaccination status before any surgery and after any deep penetrating wound

Eastern & Western Encephalomyelitis Affects all ages; uncommon in foals < 3 mos Viral infection Spread by ticks & mosquitoes; wild birds & rodents are reservoirs Seasonal and geographic disease; year to year variation based on rainfall and temperatures

EEE / WEE Vaccine is safe and effective; USE IT Foals receive an initial series of 3 doses beginning at 4 – 6 months of age Booster 1 - 2 (3) times/yr depending on risk of disease and length of mosquito season Booster before mosquito season begins Insect control

Potomac Horse Fever: Distribution Cases reported in over 40 states, Canada and Europe Disease appears to be spreading Cases tend to occur near bodies of water

Potomac Horse Fever Vaccination Commercial vaccines contain an older strain of PHF; Field strains of E. risticii continue to change More than 28 new E. risticii isolates have been identified in field cases of PHF Vaccinated horses often showed a milder form of PHF when exposed Adults: Vaccinate once or twice a year depending on risk of disease and length of vector season Booster pregnant mares 4 – 8 wks pre-foaling

Rabies: Important Facts It is a ZOONOTIC DISEASE that can be spread from animal to man as well as from animal to animal Public health concern No treatment available once neurologic signs develop Vaccinate ALL horses

Rabies Vaccine Killed intramuscular vaccine: safe, effective Duration of immunity at least 1 yr; annual boosters recommended Unvaccinated animals: primary series of 2 doses Colostral antibodies interfere with foal’s immune response: Foals born to vaccinated mares: 1st dose at 6mo, 2nd dose 1 mo later, 3rd dose at 1yr of age

West Nile Virus Vaccination Initial series of 2 vaccinations followed by a booster every 6 – 12 months depending on risk and length of mosquito season Mosquito control Remove areas of standing water

Rotavirus: MDA Highly contagious Fecal-oral transmission Damages tips of villi in SI; self-limiting Vaccinate pregnant mares: mos 8, 9, 10; repeat for each pregnancy; no “annual booster” Herd immunity waxes and wanes

Botulism: Vaccine is safe and effective Protect foal by vaccinating mare & ensuring foal ingests adequate colostrum Initial series of 3 doses given to 4 – 6 wks apart; administer during last trimester Thereafter, annual booster for mares 4 – 8 wks pre-foaling Can begin foal vaccinations at 3 – 4 mos if risk of disease is high Series of 3 doses given 4 wks apart Foal relies on MDA for protection against “Shaker Foal” syndrome