MOBILE VIEW  | 

VETERINARY VACCINES-LIVE

Classification   |    Detailed evidence-based information

Therapeutic Toxic Class

    A) Note: For information about killed veterinary vaccines, see the "VETERINARY VACCINES, KILLED" management. Commonly used modified live veterinary vaccines (Plumb, 1989; Kirk, 1986; Kirk, 1989; Talbot, 1990):
       VACCINE TYPE       TYPICAL TRADE  INTENDED  KILLED*
    (INFECTING ORGANISM)   NAMES/ MFG.    SPECIES  VACCINE
    ------------------------------------------------------
    A.  ANTHRAX BACILLUS      ---           cattle    N
    B.  BOVINE VIRAL
          DIARRHEA          Triangle        cattle    Y
    C.  BRUCELLA ABORTUS,     ---           cattle    Y
          STRAIN 19
    ------------------------------------------------------
    D.  BRUCELLA OVIS         ---           sheep     Y
    E.  BLUETONGUE            ---           sheep     N
    F.  CANINE DISTEMPER    Vanguard        dogs      N
    ------------------------------------------------------
    G.  CHLAMYDIA PSITTACI  Psittacoid      cats      N
                              ---           sheep     Y
    H.  ENCEPHALOMYELITIS,    ---           horses    Y
           EQUINE
    I.  INFECTIOUS BURSAL     ---           chickens  Y
          DISEASE
    ------------------------------------------------------
    J.  NEWCASTLE DISEASE     ---           chickens  Y
          VIRUS
    K.  OVINE ECTHYMA         ---           sheep     N
    ------------------------------------------------------
    L.  PASTEURELLA HEMOLYTICA Precon       cattle    N
    M.  PSEUDORABIES      Farrowsure        swine     Y
    ------------------------------------------------------
    N.  RABIES            Endurall-K,       dogs,     Y
                          others            cats
    O.  RHINOTRACHEITIS,  Triangle -        cattle    Y
                          killed,
          BOVINE          all others - live
    ------------------------------------------------------
    P.  RHINOTRACHEITIS/  Felocell          cats      N
          CALICIVIRUS/
          PANLEUKOPENIA,
          FELINE
    Q.  ROTAVIRUS/        Calf-guard        calves    N
          CORONAVIRUS,
          BOVINE
    *Killed Vaccine Also Available
    
       VACCINE TYPE       TYPICAL TRADE  INTENDED  KILLED*
    (INFECTING ORGANISM)   NAMES/ MFG.    SPECIES  VACCINE
    ------------------------------------------------------
    A.  ANTHRAX BACILLUS      ---           cattle    N
    B.  BOVINE VIRAL
          DIARRHEA          Triangle        cattle    Y
    C.  BRUCELLA ABORTUS,     ---           cattle    Y
          STRAIN 19
    ------------------------------------------------------
    D.  BRUCELLA OVIS         ---           sheep     Y
    E.  BLUETONGUE            ---           sheep     N
    F.  CANINE DISTEMPER    Vanguard        dogs      N
    ------------------------------------------------------
    G.  CHLAMYDIA PSITTACI  Psittacoid      cats      N
                              ---           sheep     Y
    H.  ENCEPHALOMYELITIS,    ---           horses    Y
           EQUINE
    I.  INFECTIOUS BURSAL     ---           chickens  Y
          DISEASE
    ------------------------------------------------------
    J.  NEWCASTLE DISEASE     ---           chickens  Y
          VIRUS
    K.  OVINE ECTHYMA         ---           sheep     N
    ------------------------------------------------------
    L.  PASTEURELLA HEMOLYTICA Precon       cattle    N
    M.  PSEUDORABIES      Farrowsure        swine     Y
    ------------------------------------------------------
    N.  RABIES            Endurall-K,       dogs,     Y
                          others            cats
    O.  RHINOTRACHEITIS,  Triangle -        cattle    Y
                          killed,
          BOVINE          all others - live
    ------------------------------------------------------
    P.  RHINOTRACHEITIS/  Felocell          cats      N
          CALICIVIRUS/
          PANLEUKOPENIA,
          FELINE
    Q.  ROTAVIRUS/        Calf-guard        calves    N
          CORONAVIRUS,
          BOVINE
    *Killed Vaccine Also Available
    
       VACCINE TYPE       TYPICAL TRADE  INTENDED  KILLED*
    (INFECTING ORGANISM)   NAMES/ MFG.    SPECIES  VACCINE
    ------------------------------------------------------
    A.  ANTHRAX BACILLUS      ---           cattle    N
    B.  BOVINE VIRAL
          DIARRHEA          Triangle        cattle    Y
    C.  BRUCELLA ABORTUS,     ---           cattle    Y
          STRAIN 19
    ------------------------------------------------------
    D.  BRUCELLA OVIS         ---           sheep     Y
    E.  BLUETONGUE            ---           sheep     N
    F.  CANINE DISTEMPER    Vanguard        dogs      N
    ------------------------------------------------------
    G.  CHLAMYDIA PSITTACI  Psittacoid      cats      N
                              ---           sheep     Y
    H.  ENCEPHALOMYELITIS,    ---           horses    Y
           EQUINE
    I.  INFECTIOUS BURSAL     ---           chickens  Y
          DISEASE
    ------------------------------------------------------
    J.  NEWCASTLE DISEASE     ---           chickens  Y
          VIRUS
    K.  OVINE ECTHYMA         ---           sheep     N
    ------------------------------------------------------
    L.  PASTEURELLA HEMOLYTICA Precon       cattle    N
    M.  PSEUDORABIES      Farrowsure        swine     Y
    ------------------------------------------------------
    N.  RABIES            Endurall-K,       dogs,     Y
                          others            cats
    O.  RHINOTRACHEITIS,  Triangle -        cattle    Y
                          killed,
          BOVINE          all others - live
    ------------------------------------------------------
    P.  RHINOTRACHEITIS/  Felocell          cats      N
          CALICIVIRUS/
          PANLEUKOPENIA,
          FELINE
    Q.  ROTAVIRUS/        Calf-guard        calves    N
          CORONAVIRUS,
          BOVINE
    *Killed Vaccine Also Available
    

Specific Substances

    1) VETERINARY VACCINES, LIVE ATTENUATED
    2) VETERINARY VACCINES, MODIFIED LIVE VETERINARY
    3) BIOLOGICAL PRODUCTS, LIVE ATTENUATED
    4) VACCINES, VETERINARY, LIVE

Available Forms Sources

    A) FORMS
    1) These agents are available from multiple sources. They are usually supplied as single dose or multiple dose vials, sometimes requiring reconstitution or dilution before use.

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Little data are available regarding the adverse human effects of most veterinary biological agents. Hypersensitivity reactions, local tissue injury, and infection by live attenuated viral or bacterial agents are the most commonly reported events. Used needles present risk linked to puncture wounds.
    B) The following LIVE VACCINE preparations have been reported to be PATHOGENIC (have caused active disease) in humans exposed to them: Newcastle disease live virus vaccine, Brucella abortus live strain 19, and Ovine ecthyma live virus vaccine; and modified live virus rabies vaccine preparation in a laboratory.
    1) Animals are commonly vaccinated with live vaccines for the following infectious diseases, but there are no case reports of infectious disease following human exposure to these animal vaccines: Anthrax; Feline pneumonitis (chlamydia); Equine encephalomyelitis; Bluetongue; Infectious Bursal Disease; Pasteurella hemolytica; Pseudorabies; Infectious Bovine Rhinotracheitis; Feline Viral Rhinotracheitis, Calicivirus, Panleukopenia; Bovine Rotavirus, Coronavirus; Bovine Viral Diarrhea; Canine Distemper, Adenovirus 2, Parvovirus, Parainfluenza.
    2) Note: All modified live brucella vaccines are considered to be infective in non-target species.
    C) Egg proteins may be found in various vaccines due to vaccine propagation in eggs. Egg proteins can be potentially reactive/allergenic.
    D) Modified live vaccines may contain antigens from the animal or avian cell culture used to grow the virus.
    E) Various antibiotics are found in many vaccines, used as a preservative.
    F) Vaccines that are modified live bacteria can cause disease in humans. For example, modified live organism vaccines for brucellosis have a history of causing infections in humans.
    G) Modified live viruses of zoonotic viral vaccines may cause disease in humans.
    H) A variety of adjuvants are used in animal vaccines and these may cause severe tissue reactions.
    I) Exposure to live organisms of known zoonotic diseases, and adjuvants used under laboratory conditions, should be evaluated in detail for risk to the exposed patient.
    0.2.3) VITAL SIGNS
    A) Fever may occur as a result of active infections with live agents, or due to secondary infection of a wound site. Tachycardia, hypotension, and respiratory distress may occur following anaphylactoid reaction as a consequence of hypersensitivity.
    0.2.4) HEENT
    A) BRUCELLA ABORTUS LIVE STRAIN 19 - This vaccine has caused clinical brucellosis and keratoconjunctivitis following splashing into the eye.
    B) NEWCASTLE DISEASE LIVE VIRUS - This modified live virus vaccine has caused conjunctivitis following human infection.
    0.2.5) CARDIOVASCULAR
    A) Severe hypersensitivity reaction can cause tachycardia and hypotension.
    0.2.6) RESPIRATORY
    A) Bronchospasm and respiratory distress may be noted as part of a significant hypersensitivity reaction.
    B) BRUCELLA ABORTUS LIVE STRAIN 19 VACCINE - Clinical brucellosis may cause cough and coryza.
    0.2.7) NEUROLOGIC
    A) Following exposure to MODIFIED LIVE RABIES VIRUS VACCINE (but not following exposure to killed rabies vaccine), human infection with rabies virus has been reported. The risk of infection will vary with the method(s) used to attenuate the rabies virus. Organisms used in the laboratory present a higher risk.
    B) Following infection with NEWCASTLE DISEASE LIVE VIRUS, encephalitis may occur rarely. Risk is associated with vaccine manufacturing and personnel handling the virus in the laboratory.
    0.2.13) HEMATOLOGIC
    A) NEWCASTLE DISEASE LIVE VIRUS - Rarely, human infection with this agent may cause hemolytic anemia.
    0.2.14) DERMATOLOGIC
    A) Local ischemia and/or dermal manifestations of hypersensitivity have been reported. Diseases such as cowpox and orf can be transmitted to humans. A modified live virus vaccine for these diseases may present some risk.
    0.2.15) MUSCULOSKELETAL
    A) BRUCELLA ABORTUS LIVE STRAIN 19 - This has been reported to cause arthralgias following human contact, most commonly delayed hours to days in onset.
    B) OIL ADJUVANT-CONTAINING PRODUCTS - these may cause severe vasospasm following injection, sufficient to cause tissue necrosis, particularly when injected into a finger or tendon sheaths.
    C) ALUM ADJUVANT or ALUMINUM HYDROXIDE ADJUVANT-CONTAINING PRODUCTS - an intense dose-related inflammatory reaction may occur in some patients.
    0.2.19) IMMUNOLOGIC
    A) Hypersensitivity reactions, both local and systemic, may follow exposure to veterinary biologicals. Serum sickness-like reactions, which may be delayed up to 2 weeks, may follow parenteral exposure to animal-derived products.
    B) BRUCELLA ABORTUS LIVE STRAIN 19 exposure may result in more rapid onset of symptoms and a more severe clinical course following re-exposure.
    C) NEWCASTLE DISEASE LIVE VIRUS infection in humans and other modified live organisms may cause lymphadenitis. Immune-compromised people may be more susceptible.

Laboratory Monitoring

    A) Serial titer measurements may serve to document infection if it occurs following live vaccine exposure. Multiple testing 2 or 3 weeks apart are required to show change in titer.
    B) BRUCELLA ABORTUS LIVE STRAIN 19 - Following exposure, an immediate titer measurement may document the preexisting state of immunity. This information may assist in prediction of rapidity of disease onset as well as severity of symptoms.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) Some diseases have prophylactic protocols (e.g. rabies). Risk must be established and the physician must immediately decide if the prophylactic treatment should be implemented.
    B) Where substantial oral exposure has occurred with live vaccines, particularly those intended for oral administration, GI decontamination should be considered. No data are available regarding the efficacy of activated charcoal following ingestion of these agents and should not be considered effective against potentially virulent organisms.
    C) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
    D) ANAPHYLAXIS - mild cases (urticaria only) may be treated with antihistamines with or without epinephrine. Treatment of severe cases includes oxygen supplementation, aggressive airway management (may need intubation), epinephrine, ECG monitoring, and IV fluids (if hypotensive).
    E) Information regarding treatment following exposure to most agents is limited. Treatment should be supportive and directed at existing symptoms. Hypersensitivity reactions may occur. Infection may follow exposure to live vaccines containing known zoonotic organisms.
    0.4.3) INHALATION EXPOSURE
    A) BRUCELLA ABORTUS LIVE STRAIN 19 - has been demonstrated to cause infection and/or sensitization following aerosol exposure. Other LIVE VACCINES and VACCINES INTENDED FOR AEROSOLIZATION would be expected to be likely sensitizers and with a low order of infectivity. Products for animal use are generally unit dose and the route of administration is intranasal with a syringe with an attached diffuser.
    B) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
    0.4.4) EYE EXPOSURE
    A) BRUCELLA ABORTUS LIVE STRAIN 19 - has been demonstrated to be infectious and to cause keratoconjunctivitis following ocular exposure. Immediate irrigation to reduce the extent of exposure would seem indicated. Antibiotics, that are effective for modified live bacteria (e.g. Brucella spp.), may be used.
    B) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) Infection and/or sensitization may occur through skin lesions (both recognized and unrecognized minor skin breaks) following topical dermal exposure. Careful cleansing of the area is warranted. OVINE ECTHYMA LIVE VIRUS VACCINE - has been demonstrated to cause cutaneous human infection in some cases following exposure.
    2) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    0.4.6) PARENTERAL EXPOSURE
    A) Where transdermal PUNCTURE WOUNDS may have occurred, tetanus prophylaxis and other management procedures for puncture wounds should also be considered.
    B) If the injected material contains an OIL ADJUVANT, the patient should receive immediate medical evaluation. If significant vasospasm or a compartment syndrome occurs, incision of the area with intraoperative irrigation of all affected tissue planes has been recommended.
    C) If the injected material contains an ALUM ADJUVANT or ALUMINUM HYDROXIDE ADJUVANT, an intense inflammatory reaction may occur in some patients. If such a reaction occurs, anti-inflammatory therapy may be desirable, including oral or parenteral use of nonsteroidal antiinflammatory agents (e.g., prednisone, methylprednisolone).
    D) ALLERGIC REACTION - mild cases (urticaria only) may be treated with antihistamines with or without epinephrine. Treatment of severe cases includes oxygen supplementation, aggressive airway management (may need intubation), epinephrine, ECG monitoring, and IV fluids (if hypotensive).
    E) Information regarding treatment following exposure to most agents is limited. Treatment should be supportive and directed at existing symptoms. Hypersensitivity reactions may occur. Infection may follow exposure to live vaccines.

Range Of Toxicity

    A) The number of live infectious particles to cause human illness has not been established.

Summary Of Exposure

    A) Little data are available regarding the adverse human effects of most veterinary biological agents. Hypersensitivity reactions, local tissue injury, and infection by live attenuated viral or bacterial agents are the most commonly reported events. Used needles present risk linked to puncture wounds.
    B) The following LIVE VACCINE preparations have been reported to be PATHOGENIC (have caused active disease) in humans exposed to them: Newcastle disease live virus vaccine, Brucella abortus live strain 19, and Ovine ecthyma live virus vaccine; and modified live virus rabies vaccine preparation in a laboratory.
    1) Animals are commonly vaccinated with live vaccines for the following infectious diseases, but there are no case reports of infectious disease following human exposure to these animal vaccines: Anthrax; Feline pneumonitis (chlamydia); Equine encephalomyelitis; Bluetongue; Infectious Bursal Disease; Pasteurella hemolytica; Pseudorabies; Infectious Bovine Rhinotracheitis; Feline Viral Rhinotracheitis, Calicivirus, Panleukopenia; Bovine Rotavirus, Coronavirus; Bovine Viral Diarrhea; Canine Distemper, Adenovirus 2, Parvovirus, Parainfluenza.
    2) Note: All modified live brucella vaccines are considered to be infective in non-target species.
    C) Egg proteins may be found in various vaccines due to vaccine propagation in eggs. Egg proteins can be potentially reactive/allergenic.
    D) Modified live vaccines may contain antigens from the animal or avian cell culture used to grow the virus.
    E) Various antibiotics are found in many vaccines, used as a preservative.
    F) Vaccines that are modified live bacteria can cause disease in humans. For example, modified live organism vaccines for brucellosis have a history of causing infections in humans.
    G) Modified live viruses of zoonotic viral vaccines may cause disease in humans.
    H) A variety of adjuvants are used in animal vaccines and these may cause severe tissue reactions.
    I) Exposure to live organisms of known zoonotic diseases, and adjuvants used under laboratory conditions, should be evaluated in detail for risk to the exposed patient.

Vital Signs

    3.3.1) SUMMARY
    A) Fever may occur as a result of active infections with live agents, or due to secondary infection of a wound site. Tachycardia, hypotension, and respiratory distress may occur following anaphylactoid reaction as a consequence of hypersensitivity.
    3.3.2) RESPIRATIONS
    A) Bronchospasm and/or respiratory distress may occur as part of an anaphylactoid reaction.
    3.3.3) TEMPERATURE
    A) BRUCELLA ABORTUS LIVE STRAIN 19 - Fever may occur within hours after inoculation in previously sensitized individuals (Bardenwerper, 1954). In other individuals, onset of fever may be delayed as long as 6 weeks (Sadusk et al, 1957).
    B) NEWCASTLE DISEASE LIVE VIRUS - Low-grade fever is a characteristic finding in human infection with this agent (Dardiri et al, 1962; Trott & Ploworth, 1965; Nelson et al, 1952).
    3.3.4) BLOOD PRESSURE
    A) Anaphylactoid reactions might be expected to result in hypotension in some individuals.
    3.3.5) PULSE
    A) Tachycardia might be expected as part of a hypersensitivity reaction.

Heent

    3.4.1) SUMMARY
    A) BRUCELLA ABORTUS LIVE STRAIN 19 - This vaccine has caused clinical brucellosis and keratoconjunctivitis following splashing into the eye.
    B) NEWCASTLE DISEASE LIVE VIRUS - This modified live virus vaccine has caused conjunctivitis following human infection.
    3.4.3) EYES
    A) BRUCELLA ABORTUS LIVE STRAIN 19 - Splashing or spraying of this vaccine into the eyes has been reported in at least 4 cases. One resulted in keratoconjunctivitis with reexacerbations following handling of the vaccine. Three of the 4 individuals developed bacteremia (Van Rooyen, 1981; Sadusk et al, 1957).
    B) NEWCASTLE DISEASE LIVE VIRUS - Human infection with this agent characteristically demonstrates conjunctivitis (Dardiri et al, 1962; Trott & Ploworth, 1965; Nelson et al, 1952).
    C) Irritation may occur following direct exposure.
    D) Conjunctivitis may occur as part of a hypersensitivity response.

Cardiovascular

    3.5.1) SUMMARY
    A) Severe hypersensitivity reaction can cause tachycardia and hypotension.
    3.5.2) CLINICAL EFFECTS
    A) TACHYARRHYTHMIA
    1) Tachycardia and/or hypotension may develop as part of an anaphylactoid response.

Respiratory

    3.6.1) SUMMARY
    A) Bronchospasm and respiratory distress may be noted as part of a significant hypersensitivity reaction.
    B) BRUCELLA ABORTUS LIVE STRAIN 19 VACCINE - Clinical brucellosis may cause cough and coryza.
    3.6.2) CLINICAL EFFECTS
    A) BRONCHOSPASM
    1) Bronchospasm and/or respiratory distress may occur as part of an anaphylactoid response.
    B) ACUTE RESPIRATORY INFECTIONS
    1) BRUCELLA ABORTUS LIVE STRAIN 19 - Clinical brucellosis may be manifested as coryza and cough, along with conjunctivitis. Systemic disease can also occur.

Neurologic

    3.7.1) SUMMARY
    A) Following exposure to MODIFIED LIVE RABIES VIRUS VACCINE (but not following exposure to killed rabies vaccine), human infection with rabies virus has been reported. The risk of infection will vary with the method(s) used to attenuate the rabies virus. Organisms used in the laboratory present a higher risk.
    B) Following infection with NEWCASTLE DISEASE LIVE VIRUS, encephalitis may occur rarely. Risk is associated with vaccine manufacturing and personnel handling the virus in the laboratory.
    3.7.2) CLINICAL EFFECTS
    A) INFECTIOUS DISEASE
    1) RABIES VACCINE, MODIFIED LIVE VIRUS - Human infection following exposure has been reported but is probably infrequent. The case reported by these authors involved inhalational exposure in a laboratory to a modified live virus rabies vaccine (Tillotson et al, 1977).
    2) ACUTE BRUCELLOSIS - has developed in veterinarians after accidental injection of the modified live organism vaccine (Wilkins & Bowman, 1997; Squarcione et al, 1990).
    B) MENINGITIS
    1) BRUCELLA ABORTUS LIVE STRAIN 19 VACCINE - Meningitis has been reported following exposure in a laboratory. Aerosol transmission by fomites was implicated as the route of infection (Montes et al, 1986)
    C) ENCEPHALITIS
    1) NEWCASTLE DISEASE LIVE VIRUS - Encephalitis has been reported following human infection with this agent, but appears to be uncommon (Dardiri et al, 1962; Beran, 1981).

Hematologic

    3.13.1) SUMMARY
    A) NEWCASTLE DISEASE LIVE VIRUS - Rarely, human infection with this agent may cause hemolytic anemia.
    3.13.2) CLINICAL EFFECTS
    A) LEUKOCYTOSIS
    1) Leukocytosis may be associated with either hypersensitivity reactions or active infection.
    B) HEMOLYTIC ANEMIA
    1) NEWCASTLE DISEASE LIVE VIRUS - Hemolytic anemia is an uncommon event during human infection with this agent (Dardiri et al, 1962; Beran, 1981).

Dermatologic

    3.14.1) SUMMARY
    A) Local ischemia and/or dermal manifestations of hypersensitivity have been reported. Diseases such as cowpox and orf can be transmitted to humans. A modified live virus vaccine for these diseases may present some risk.
    3.14.2) CLINICAL EFFECTS
    A) URTICARIA
    1) Dermal manifestations of hypersensitivity may be noted, including pruritus with hives (Crosby et al, 1986).
    B) INFECTION OF SKIN
    1) OVINE ECTHYMA LIVE VIRUS VACCINE - Human infection has been reported following exposure to this vaccine. Skin lesions on the head and arms have been described, and "usually such infections are not serious" (Colorado Serum Co, 1988).
    C) SKIN ULCER
    1) OIL ADJUVANT-CONTAINING VACCINES - these products may result in local skin sloughing as well as deep underlying injury (CSM, 1987).
    2) Accidental injection of oil based veterinary vaccines has caused soft tissue inflammation, tissue necrosis, granulomas, sterile abscesses, and local ulceration (Jones, 1996).

Musculoskeletal

    3.15.1) SUMMARY
    A) BRUCELLA ABORTUS LIVE STRAIN 19 - This has been reported to cause arthralgias following human contact, most commonly delayed hours to days in onset.
    B) OIL ADJUVANT-CONTAINING PRODUCTS - these may cause severe vasospasm following injection, sufficient to cause tissue necrosis, particularly when injected into a finger or tendon sheaths.
    C) ALUM ADJUVANT or ALUMINUM HYDROXIDE ADJUVANT-CONTAINING PRODUCTS - an intense dose-related inflammatory reaction may occur in some patients.
    3.15.2) CLINICAL EFFECTS
    A) JOINT PAIN
    1) BRUCELLA ABORTUS LIVE STRAIN 19 VACCINE - Arthralgia has been reported following an accidental needle stick of the knee with a vaccine-contaminated needle, in a previously sensitized individual (Price, 1973).
    B) PERIPHERAL ISCHEMIA
    1) OIL ADJUVANT-CONTAINING VACCINES - these products have been reported to "cause intense vascular spasm". This may be so severe that entire digits or tendons may be compromised (CSM, 1987). The injected material itself may result in local pressure build-up, particularly after the development of local edema.
    C) INJECTION SITE INFLAMMATION
    1) ALUM ADJUVANT or ALUMINUM HYDROXIDE-CONTAINING VACCINES - A variety of adjuvants are used in animal vaccines. These products may cause an intense inflammatory response, particularly at the site of injection. At appropriate doses, this is an intended response resulting in enhanced production of immunity. However, with variation in response between species and between products, an exaggeration of the desired pharmacologic effect of the adjuvant may occur, resulting in toxic effects. Therapy should be directed at reducing the inflammatory response, where clinically appropriate. Effective agents may include non-steroidal antiinflammatory agents (such ibuprofen or naproxen) and/or corticosteroids (such as prednisone or methylprednisolone). Laboratory preparations may use a complete adjuvant (contains tuberculin).
    2) Local swelling, severe pain, blisters, and deep ulceration exposing flexor tendons developed after accidental injection of Brucella abortus S.19 vaccine into the proximal interphalangeal (PIP) joint of a finger (Harvey, 1969). Healing required several months and the patient was left with no movement at the DIP and 75% movement at the PIP.

Immunologic

    3.19.1) SUMMARY
    A) Hypersensitivity reactions, both local and systemic, may follow exposure to veterinary biologicals. Serum sickness-like reactions, which may be delayed up to 2 weeks, may follow parenteral exposure to animal-derived products.
    B) BRUCELLA ABORTUS LIVE STRAIN 19 exposure may result in more rapid onset of symptoms and a more severe clinical course following re-exposure.
    C) NEWCASTLE DISEASE LIVE VIRUS infection in humans and other modified live organisms may cause lymphadenitis. Immune-compromised people may be more susceptible.
    3.19.2) CLINICAL EFFECTS
    A) ACUTE ALLERGIC REACTION
    1) Most veterinary biological products are potential sensitizers. As they are comprised of animal proteins, they may stimulate immunoglobulin production to the contained proteins and thereby set the stage for future hypersensitivity reactions.
    2) Many also contain penicillin, streptomycin, phenol and/or thimerosal (Colorado Serum Co, 1988). Individuals who have already been sensitized to these agents may be at increased risk of hypersensitivity reactions. Others are at risk of becoming sensitized to these agents.
    3) Many vaccines are propagated in embryonated eggs and, therefore, contain chicken proteins. Chicken proteins are potentially reactive and allergenic, and may sensitize the patient to certain foods.
    B) LYMPHADENOPATHY
    1) NEWCASTLE DISEASE LIVE VIRUS - Adenitis is a characteristic finding in human infection with this agent (Dardiri et al, 1962; Beran, 1981).

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Serial titer measurements may serve to document infection if it occurs following live vaccine exposure. Multiple testing 2 or 3 weeks apart are required to show change in titer.
    B) BRUCELLA ABORTUS LIVE STRAIN 19 - Following exposure, an immediate titer measurement may document the preexisting state of immunity. This information may assist in prediction of rapidity of disease onset as well as severity of symptoms.
    4.1.2) SERUM/BLOOD
    A) SPECIFIC AGENT
    1) If exposure to BRUCELLA ABORTUS STRAIN 19 VACCINE has occurred, an immediate titer measurement may document the preexisting state of immunity. This information may assist in prediction of rapidity of disease onset as well as severity of symptoms. Blood cultures for Brucella abortus should generally be obtained if fever develops, and cultures should be obtained before antibiotics are administered. .
    B) OTHER
    1) No specific laboratory studies have been proved to be of value in the management of most of these agents. Serial titer measurements may serve to document infection if it occurs following live vaccine exposure.

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) Serial titer measurements may serve to document infection if it occurs following live vaccine exposure. Multiple testing 2 or 3 weeks apart are required to show change in titer.
    B) BRUCELLA ABORTUS LIVE STRAIN 19 - Following exposure, an immediate titer measurement may document the preexisting state of immunity. This information may assist in prediction of rapidity of disease onset as well as severity of symptoms.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY
    1) Emesis is of unproven efficacy following ingestion of these products, but may be used where GI decontamination is felt warranted.
    B) ACTIVATED CHARCOAL
    1) Activated charcoal has unproven efficacy as a treatment following oral ingestion of animal vaccines.
    2) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    3) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) ACUTE ALLERGIC REACTION
    1) SUMMARY
    a) Mild to moderate allergic reactions may be treated with antihistamines with or without inhaled beta adrenergic agonists, corticosteroids or epinephrine. Treatment of severe anaphylaxis also includes oxygen supplementation, aggressive airway management, epinephrine, ECG monitoring, and IV fluids.
    2) BRONCHOSPASM
    a) ALBUTEROL
    1) ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007). CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 mg/kg (up to 10 mg) every 1 to 4 hours as needed, or 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).
    3) CORTICOSTEROIDS
    a) Consider systemic corticosteroids in patients with significant bronchospasm.
    b) PREDNISONE: ADULT: 40 to 80 milligrams/day. CHILD: 1 to 2 milligrams/kilogram/day (maximum 60 mg) in 1 to 2 divided doses divided twice daily (National Heart,Lung,and Blood Institute, 2007).
    4) MILD CASES
    a) DIPHENHYDRAMINE
    1) SUMMARY: Oral diphenhydramine, as well as other H1 antihistamines can be used as indicated (Lieberman et al, 2010).
    2) ADULT: 50 milligrams orally, or 10 to 50 mg intravenously at a rate not to exceed 25 mg/min or may be given by deep intramuscular injection. A total of 100 mg may be administered if needed. Maximum daily dosage is 400 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
    3) CHILD: 5 mg/kg/24 hours or 150 mg/m(2)/24 hours. Divided into 4 doses, administered intravenously at a rate not exceeding 25 mg/min or by deep intramuscular injection. Maximum daily dosage is 300 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
    5) MODERATE CASES
    a) EPINEPHRINE: INJECTABLE SOLUTION: It should be administered early in patients by IM injection. Using a 1:1000 (1 mg/mL) solution of epinephrine. Initial Dose: 0.01 mg/kg intramuscularly with a maximum dose of 0.5 mg in adults and 0.3 mg in children. The dose may be repeated every 5 to 15 minutes, if no clinical improvement. Most patients respond to 1 or 2 doses (Nowak & Macias, 2014).
    6) SEVERE CASES
    a) EPINEPHRINE
    1) INTRAVENOUS BOLUS: ADULT: 1 mg intravenously as a 1:10,000 (0.1 mg/mL) solution; CHILD: 0.01 mL/kg intravenously to a maximum single dose of 1 mg given as a 1:10,000 (0.1 mg/mL) solution. It can be repeated every 3 to 5 minutes as needed. The dose can also be given by the intraosseous route if IV access cannot be established (Lieberman et al, 2015). ALTERNATIVE ROUTE: ENDOTRACHEAL ADMINISTRATION: If IV/IO access is unavailable. DOSE: ADULT: Administer 2 to 2.5 mg of 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube. CHILD: DOSE: 0.1 mg/kg to a maximum of 2.5 mg administered as a 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube (Lieberman et al, 2015).
    2) INTRAVENOUS INFUSION: Intravenous administration may be considered in patients poorly responsive to IM or SubQ epinephrine. An epinephrine infusion may be prepared by adding 1 mg (1 mL of 1:1000 (1 mg/mL) solution) to 250 mL D5W, yielding a concentration of 4 mcg/mL, and infuse this solution IV at a rate of 1 mcg/min to 10 mcg/min (maximum rate). CHILD: A dosage of 0.01 mg/kg (0.1 mL/kg of a 1:10,000 (0.1 mg/mL) solution up to 10 mcg/min (maximum dose 0.3 mg) is recommended for children (Lieberman et al, 2010). Careful titration of a continuous infusion of IV epinephrine, based on the severity of the reaction, along with a crystalloid infusion can be considered in the treatment of anaphylactic shock. It appears to be a reasonable alternative to IV boluses, if the patient is not in cardiac arrest (Vanden Hoek,TL,et al).
    7) AIRWAY MANAGEMENT
    a) OXYGEN: 5 to 10 liters/minute via high flow mask.
    b) INTUBATION: Perform early if any stridor or signs of airway obstruction.
    c) CRICOTHYROTOMY: Use if unable to intubate with complete airway obstruction (Vanden Hoek,TL,et al).
    d) BRONCHODILATORS are recommended for mild to severe bronchospasm.
    e) ALBUTEROL: ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007).
    f) ALBUTEROL: CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 milligram/kilogram (maximum 10 milligrams) every 1 to 4 hours as needed OR administer 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).
    8) MONITORING
    a) CARDIAC MONITOR: All complicated cases.
    b) IV ACCESS: Routine in all complicated cases.
    9) HYPOTENSION
    a) If hypotensive give 500 to 2000 milliliters crystalloid initially (20 milliliters/kilogram in children) and titrate to desired effect (stabilization of vital signs, mentation, urine output); adults may require up to 6 to 10 L/24 hours. Central venous or pulmonary artery pressure monitoring is recommended in patients with persistent hypotension.
    1) VASOPRESSORS: Should be used in refractory cases unresponsive to repeated doses of epinephrine and after vigorous intravenous crystalloid rehydration (Lieberman et al, 2010).
    2) DOPAMINE: Initial Dose: 2 to 20 micrograms/kilogram/minute intravenously; titrate to maintain systolic blood pressure greater than 90 mm Hg (Lieberman et al, 2010).
    10) H1 and H2 ANTIHISTAMINES
    a) SUMMARY: Antihistamines are second-line therapy and are used as supportive therapy and should not be used in place of epinephrine (Lieberman et al, 2010).
    1) DIPHENHYDRAMINE: ADULT: 25 to 50 milligrams via a slow intravenous infusion or IM. PEDIATRIC: 1 milligram/kilogram via slow intravenous infusion or IM up to 50 mg in children (Lieberman et al, 2010).
    b) RANITIDINE: ADULT: 1 mg/kg parenterally; CHILD: 12.5 to 50 mg parenterally. If the intravenous route is used, ranitidine should be infused over 10 to 15 minutes or diluted in 5% dextrose to a volume of 20 mL and injected over 5 minutes (Lieberman et al, 2010).
    c) Oral diphenhydramine, as well as other H1 antihistamines, can also be used as indicated (Lieberman et al, 2010).
    11) DYSRHYTHMIAS
    a) Dysrhythmias and cardiac dysfunction may occur primarily or iatrogenically as a result of pharmacologic treatment (epinephrine) (Vanden Hoek,TL,et al). Monitor and correct serum electrolytes, oxygenation and tissue perfusion. Treat with antiarrhythmic agents as indicated.
    12) OTHER THERAPIES
    a) There have been a few reports of patients with anaphylaxis, with or without cardiac arrest, that have responded to vasopressin therapy that did not respond to standard therapy. Although there are no randomized controlled trials, other alternative vasoactive therapies (ie, vasopressin, norepinephrine, methoxamine, and metaraminol) may be considered in patients in cardiac arrest secondary to anaphylaxis that do not respond to epinephrine (Vanden Hoek,TL,et al).
    B) BRUCELLOSIS
    1) BRUCELLA ABORTUS LIVE VACCINE
    a) When exposure to Brucella abortus live strain 19 vaccine live attenuated vaccine has occurred:
    1) The patient's state of immunity to Brucella should be ascertained to the extent readily possible by history and/or lab studies.
    2) Immune individuals are more likely to display onset of symptoms within 24 hours following exposure, which may be partially indicated by a hypersensitivity reaction. If symptoms of hypersensitivity develop, some clinical benefit may be obtained by use of epinephrine, corticosteroids, and/or diphenhydramine as appropriate (Joffe & Diamond, 1966; Gulasekharam, 1970; McCullough, 1963). If corticosteroids are used, appropriate antibiotic therapy is probably also indicated (McCulloch, 1963).
    3) Appropriate antibiotic therapy should probably be employed, particularly if symptoms of infection develop. The use of a single agent has been associated with a 10 to 40 percent chance of relapse, and the use of two antibiotics simultaneously is therefore currently preferred. In the absence of central nervous system and endocardial involvement, regimens involving streptomycin have been associated with fewer relapses than regimens not including streptomycin. However, the need for long-term intramuscular administration of streptomycin is a disadvantage of its use. Blood cultures should be taken before antibiotic therapy is started.
    4) The optimal regimen remains controversial. Commonly accepted ADULT regimens for patients who are not pregnant include:
    a) DOXYCYCLINE + RIFAMPIN. Doxycycline 200 milligrams/day plus rifampin 600 milligrams/day, both given for 6 weeks, is considered a regimen of choice and has the advantage of oral administration of both agents (Mikolich & Boyce, 1990).
    b) TETRACYCLINE + STREPTOMYCIN. Tetracycline hydrochloride (40 milligrams/kilogram/day orally divided into 3 to 4 doses up to a maximum daily dose of 2000 milligrams) used for 6 weeks, together with streptomycin for 21 days, has been widely used with favorable results, in patients who are not allergic to these agents. The initial dose of streptomycin in the presence of normal renal function is 20 milligrams/kilogram up to 1 gram daily (Mikolich & Boyce, 1990). Gentamicin (in the presence of normal renal function, 5 milligrams/kilogram/day divided every 8 hours) instead of streptomycin has shown better activity in vitro and is less ototoxic, but less clinical experience exists with this agent (Salata & Ravdin, 1985). Serum aminoglycoside levels should probably be monitored where streptomycin or gentamicin are used, and dosing adjusted as indicated.
    5) In PREGNANCY, rifampin 600 - 900 milligrams/day for at least 6 weeks is considered the regimen of choice (Mikolich & Boyce, 1990).
    6) For PEDIATRIC patients under age 9, a preferred regimen is the use of at least 4-6 weeks of trimethoprim - sulfamethoxazole (10 milligrams/kilogram/day of trimethoprim and 50 milligrams/kilogram/day of sulfamethoxazole up to a daily maximum of 480 milligrams/2400 milligrams), divided in 2 doses when given orally or divided into 4 doses when given intravenously. Folinic acid given concomitantly may be required to prevent hematologic toxicity at these doses given for such a prolonged course of therapy (Salata & Ravdin, 1985; Young & Yow, 1987).
    7) Imipenem and ciprofloxacin frequently appear to have good in vitro activity against Brucella, but experience with their use in treating Brucella abortus infection is extremely limited (Mikolich & Boyce, 1990).
    C) SUPPORT
    1) Treatment should be supportive and directed at observed symptoms and abnormalities.

Inhalation Exposure

    6.7.1) DECONTAMINATION
    A) Terminate exposure as soon as possible.
    B) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
    C) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    D) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.
    6.7.2) TREATMENT
    A) ACUTE ALLERGIC REACTION
    1) Hypersensitivity reactions may occur following inhalation of foreign proteins, particularly in sensitized individuals. Treatment with corticosteroids, diphenhydramine, and/or epinephrine, as clinically appropriate, should be employed when these occur. See "ORAL/PARENTERAL EXPOSURE" section for specific recommendations.
    B) BRUCELLOSIS
    1) Live attenuated vaccines may prove infectious following inhalation. Brucella abortus strain 19 vaccine has specifically been reported to cause Brucellosis following aerosol inhalation. Treatment following Brucella abortus strain 19 vaccine exposure should follow those under "ORAL/PARENTERAL EXPOSURE" above.
    C) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).
    6.8.2) TREATMENT
    A) ACUTE ALLERGIC REACTION
    1) Hypersensitivity reaction may occur following conjunctival contact with foreign substances. Local treatment and/or systemic treatment as detailed above should be employed as clinically appropriate. See "ORAL/PARENTERAL EXPOSURE" section for specific recommendations.
    B) BRUCELLOSIS
    1) Brucella abortus strain 19 vaccine has been shown to cause clinical brucellosis following ocular exposure (Sadusk et al, 1957; Spink, 1957). Keratoconjunctivitis has also been reported following Brucella abortus strain 19 vaccine exposure to the eye (Van Rooyen, 1981). Treatment should include appropriate antibiotics, as discussed under "ORAL/PARENTERAL EXPOSURE," when infection occurs. The role of prophylactic antibiotic therapy following exposure, but before the onset of clinical disease, remains undefined at present.
    C) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) Careful cleansing of the area is warranted.
    2) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).
    6.9.2) TREATMENT
    A) ACUTE ALLERGIC REACTION
    1) Hypersensitivity reactions may develop. If so, topical and/or systemic therapy with epinephrine, corticosteroids, and/or diphenhydramine should be employed as clinically appropriate. See "ORAL/PARENTERAL EXPOSURE" section for specific recommendations.
    B) BRUCELLOSIS
    1) Brucella abortus live strain 19 vaccine has caused brucellosis following skin contact. Treatment for brucellosis is discussed above under "ORAL/PARENTERAL EXPOSURE."
    2) Ovine ecthyma live virus vaccine has been reported to cause human infection following dermal exposure. No specific treatment has been reported.
    C) Treatment should include recommendations listed in the ORAL EXPOSURE section when appropriate.

Case Reports

    A) ADVERSE EFFECTS
    1) A summary of infections acquired in veterinary research lab experience included brucellosis and Newcastle disease (Miller et al, 1987). These cases were not necessarily acquired following exposure to the veterinary vaccines, although vaccines against these diseases containing live attenuated organisms are commercially available.
    2) BRUCELLA ABORTUS LIVE STRAIN 19 VACCINE INJECTION - A 25-year-old veterinarian known to have previously developed antibodies against Brucella sustained a needle stick injury from a syringe contaminated with Brucella abortus strain 19 vaccine to the palm of his right hand. Six hours thereafter, his hand was painful and swollen. Ten hours after the injury, he was started on oral chlortetracycline 250 mg QID. By 20 hours post-injury, he was febrile to 102 degrees F and was having chills and generalized body aches. Lymphangitis was noted in the injured arm. Oral tetracycline was continued, and he defervesced by the fourth day following exposure. Blood cultures for Brucella abortus were negative, but the patient was treated with a total of 21 days of oral chlortetracycline (Spink & Thompson, 1953).
    3) A veterinarian accidentally injected 0.5 to 0.75 mL of Brucella vaccine into the volar tissue of his proximal left index finger. Within 3 hours, the finger was markedly swollen. By 6 hours following the accident, pain was so intense that he sought emergency medical care; oxytetracycline and an antihistamine were started orally. By the next day, pain continued despite the use of codeine. A compartment syndrome subsequently developed, with eventual loss of part of the soft tissue and limitation of motion in that digit (Harvey, 1969).
    4) DERMAL AND OCULAR EXPOSURE - A 50-year-old physician/rancher sprayed his face and eyes with Brucella abortus live strain 19 vaccine when the needle blew off of a non-locking syringe. Thirty-one days later, he developed anterior and posterior cervical adenopathy and posterior neck tenderness. Malaise, chills, and severe pharyngitis began 35 days following exposure. Low grade fever was first noted on day 36, followed soon thereafter by coryza, cough, and conjunctivitis. Brucella abortus strain 19 was isolated from blood drawn on the 48th day post exposure. The patient was treated with 3 weeks of oral tetracycline and 2 weeks of streptomycin (Sadusk et al, 1957).
    5) NEWCASTLE DISEASE - A 14-year-old male drank two glasses from a gallon of milk inoculated the night before with 21 vials of live Newcastle disease virus vaccine intended to immunize 1000 baby chicks. Magnesium sulfate catharsis was induced approximately 15 minutes following exposure. He remained completely asymptomatic (Crosby et al, 1986).

Summary

    A) The number of live infectious particles to cause human illness has not been established.

Therapeutic Dose

    7.2.1) ADULT
    A) GENERAL
    1) Insufficient information exists to determine the human therapeutic or toxic doses of these agents.

Pharmacologic Mechanism

    A) These agents are intended for use as immunizing agents. As such, they are extrinsic proteins or live attenuated infectious agents, which serve to sensitize the recipient to future exposure.

Toxicologic Mechanism

    A) Toxicologic responses are mediated either by undesired hypersensitivity responses upon exposure, or by the development of active infection or tissue response following exposure to live infectious agents.

Clinical Effects

    11.1.1) AVIAN/BIRD
    A) POULTRY -
    1) INFECTIOUS BURSAL DISEASE -
    a) VACCINES AVAILABLE/ZOONOTIC - Not zoonotic. Live vaccines of varying virulence and chick-embryo or cell-culture origin are available.
    b) SPECIES USED IN - Chicken
    c) TRANSMISSION/OCCURRENCE - Fecal/oral; very stable in environment
    d) ADVERSE EFFECTS OF VACCINE - Unknown
    2) NEWCASTLE DISEASE -
    a) VACCINES AVAILABLE/ZOONOTIC - Zoonotic; live culture vaccine available, which is pathogenic for humans (Schnurrenberger & Hubbert, 1981); inactivated vaccine also available
    b) SPECIES USED IN - Chicken
    c) TRANSMISSION/OCCURRENCE - Inhalation; ingestion; conjunctival contact of secretions
    d) ADVERSE EFFECTS OF VACCINE - Unknown
    11.1.2) BOVINE/CATTLE
    A) ANTHRAX -
    1) VACCINES AVAILABLE/ZOONOTIC - Zoonotic; modified live bacterin vaccine available
    2) SPECIES USED IN - Cattle
    3) TRANSMISSION/OCCURRENCE - Direct exposure to the vaccine. Anthrax is a zoonotic disease.
    4) ADVERSE EFFECTS OF VACCINE - Unknown
    B) BOVINE VIRAL DIARRHEA/BVD -
    1) VACCINES AVAILABLE/ZOONOTIC - Not zoonotic. Modified live vaccines are available.
    2) SPECIES USED IN - Cattle
    3) TRANSMISSION/OCCURRENCE - Direct contact
    4) ADVERSE EFFECTS OF VACCINE - BVD is teratogenic (Fenner, 1987).
    C) BRUCELLOSIS -
    1) VACCINES AVAILABLE/ZOONOTIC - Zoonotic; B. abortus strain 19 bacterin vaccine is live culture and pathogenic for humans (Schnurrenberger & Hubbert, 1981); Brucella vaccine strain 45/20 bacterin (killed) is used in Australia
    2) SPECIES USED IN - Cattle
    3) TRANSMISSION/OCCURRENCE - Direct contact with the vaccine.
    4) ADVERSE EFFECTS OF VACCINE - Femorotibial arthropathy and persistent serological reactions have been reported in cows vaccinated in calfhood with B. abortus strain 19 vaccine (Corbel et al, 1989).
    D) INFECTIOUS BOVINE RHINOTRACHEITIS -
    1) VACCINES AVAILABLE/ZOONOTIC - Not zoonotic. Modified live vaccines are available.
    2) SPECIES USED IN - Cattle
    3) TRANSMISSION/OCCURRENCE - Direct contact
    4) ADVERSE EFFECTS OF VACCINE - Many IBR vaccines are abortigenic.
    E) PASTEURELLA HEMOLYTICA -
    1) VACCINES AVAILABLE/ZOONOTIC - Pasteurellosis is zoonotic. Modified live bacterin is available.
    2) SPECIES USED IN - Cattle
    3) TRANSMISSION/OCCURRENCE - Direct contact with the vaccine.
    4) ADVERSE EFFECTS OF VACCINE - Unknown
    F) ROTAVIRUS/CORONAVIRUS -
    1) VACCINES AVAILABLE/ZOONOTIC - Zoonotic; modified live vaccine available
    2) SPECIES USED IN - Juvenile cattle
    3) TRANSMISSION/OCCURRENCE - Direct contact with the vaccine. The virus is relatively species-specific.
    4) ADVERSE EFFECTS OF VACCINE - Unknown
    11.1.3) CANINE/DOG
    A) DA2PPL/DISTEMPER BOOSTER -
    1) VACCINES AVAILABLE/ZOONOTIC - Leptospirosis portion is zoonotic. Canine distemper, parainfluenza, canine parvovirus, and canine hepatitis are not zoonotic. Combinations of modified live vaccines are available.
    2) SPECIES USED IN - Dogs
    3) TRANSMISSION/OCCURRENCE - Direct contact
    4) ADVERSE EFFECTS OF VACCINE -
    a) Postvaccinal distemper has been associated with vaccination with canine distemper modified live vaccine.
    b) "Blue eye," anterior uveitis and subclinical interstitial nephritis (an arthus reaction) occur in less than 1% of dogs vaccinated with canine adenovirus type 1. Currently used canine vaccines now contain canine adenovirus type 2, that is not associated with the reaction.
    c) Modified live vaccines should not be used in general in pregnant animals because of the risk of inducing abortion, resorption, or malformations.
    1) Abortion and death occurred in 3 bitches due to bluetongue virus contamination of the vaccine given in late pregnancy. Abortion occurred 1 to 6 days post-vaccination, death occurred 8 to 12 days post- vaccination. Death of the bitches was due to diffuse interstitial pneumonia and inflammation of the vascular endothelium of many organs (Evermann JF, McKiernan AJ, Wilbur LA, et al, 1995).
    d) Focal necrotizing granulomatous panniculitis has been associated with subcutaneous injection of rabies vaccine in dogs and cats (Hendrick & Dunagan, 1991).
    B) RABIES -
    1) VACCINES AVAILABLE/ZOONOTIC - Zoonotic; modified live and killed vaccines available
    2) SPECIES USED IN - Dogs and cats
    3) TRANSMISSION/OCCURRENCE - Direct contact with the vaccine.
    4) ADVERSE EFFECTS OF VACCINE - Focal necrotizing granulomatous panniculitis has been associated with subcutaneous injection of rabies vaccine in dogs and cats (Hendrick & Dunagen, 1991). Vaccination failures have been reported in Nigerian dogs given chicken embryo origin, low passage vaccine (Okolo, 1989).
    11.1.6) FELINE/CAT
    A) CHLAMYDIA -
    1) VACCINES AVAILABLE/ZOONOTIC - Zoonotic; modified live bacterin available. Killed vaccine is used in sheep.
    2) SPECIES USED IN - Cats, sheep
    3) TRANSMISSION/OCCURRENCE - Direct contact with the vaccine.
    4) ADVERSE EFFECTS OF VACCINE - Unknown
    B) FVRCP/FELINE DISTEMPER BOOSTER -
    1) VACCINES AVAILABLE/ZOONOTIC - Feline panleukopenia, feline viral rhinotracheitis, and calicivirus are not zoonotic. A combination of modified live virus vaccines is available.
    2) SPECIES USED IN - Cat
    3) TRANSMISSION/OCCURRENCE - Direct contact
    4) ADVERSE EFFECTS OF VACCINE -
    a) Modified live vaccines should not be used in general in pregnant animals because of the risk of inducing abortion, resorption, or malformations. Feline panleukopenia vaccine is tetratogenic (Fenner, 1987).
    b) Cerebellar degeneration may occur in kittens vaccinated for feline panleukopenia at less than 4 weeks of age (Greene CE and Braund KG, 1989).
    c) The intranasal vaccine for FVR may cause sneezing and ocular discharge (Mansfield, 1996).
    d) Accidental skin contamination with attenuated FVR vaccine can cause signs of the infection if the cat licks at the injection site. This may also occur if the nose or mouth are inadvertently exposed to the vaccine (Mansfield, 1996).
    C) RABIES -
    1) VACCINES AVAILABLE/ZOONOTIC - Zoonotic; modified live and killed vaccines available
    2) SPECIES USED IN - Dogs and cats; killed vaccine used in a large number of animal species.
    3) TRANSMISSION/OCCURRENCE - Direct contact with the vaccine.
    4) ADVERSE EFFECTS OF VACCINE - Focal necrotizing granulomatous panniculitis has been associated with subcutaneous injection of rabies vaccine in dogs and cats (Hendrick & Dunagan, 1991).
    11.1.9) OVINE/SHEEP
    A) BLUETONGUE -
    1) VACCINES AVAILABLE/ZOONOTIC - May be zoonotic. Modified live vaccines are available.
    2) SPECIES USED IN - Sheep
    3) TRANSMISSION/OCCURRENCE - Direct contact with the vaccine
    4) ADVERSE EFFECTS OF VACCINE - Bluetongue vaccine is teratogenic.
    B) OVINE ECTHYMA -
    1) VACCINES AVAILABLE/ZOONOTIC - Zoonotic. Modified live vaccine available
    2) SPECIES USED IN - Sheep
    3) TRANSMISSION/OCCURRENCE - Direct contact with the vaccine.
    4) ADVERSE EFFECTS OF VACCINE - Unknown
    11.1.10) PORCINE/SWINE
    A) PSEUDORABIES -
    1) VACCINES AVAILABLE/ZOONOTIC - Not zoonotic. Modified live vaccines are available.
    2) SPECIES USED IN - Swine
    3) TRANSMISSION/OCCURRENCE - Direct contact
    4) ADVERSE EFFECTS OF VACCINE - Unknown
    11.1.13) OTHER
    A) OTHER
    1) FERRETS -
    a) DISTEMPER -
    1) VACCINES AVAILABLE/ZOONOTIC - Not zoonotic. Modified live vaccine available for subcutaneous use in ferrets (Fervac-D, United Vaccines, Madison, Wisconsin).
    2) SPECIES USED IN - Ferret
    3) TRANSMISSION OCCURRENCE - Transmission is by aerosol and direct contact.
    4) ADVERSE EFFECTS OF VACCINE - Unknown
    b) RABIES -
    1) VACCINES AVAILABLE/ZOONOTIC - Zoonotic; modified live and killed vaccines available
    2) SPECIES USED IN - Dogs and cats; ferrets
    3) TRANSMISSION/OCCURRENCE - Direct contact with the vaccine.
    4) ADVERSE EFFECTS OF VACCINE - No rabies vaccine has been FDA approved for use in ferrets. One of 13 documented cases of domestic ferret rabies in the USA between 1954 and 1985 may have been associated with vaccination with a modified live rabies vaccine (Hoover et al, 1989).

Treatment

    11.2.1) SUMMARY
    A) GENERAL TREATMENT
    1) Begin treatment immediately.
    2) Remove the patient and other animals from the source of contamination.
    3) ANAPHYLAXIS -
    a) The use of any biological, such as vaccines, may cause an anaphylactoid reaction. Vaccines should not be administered outside of a medical environment unless the necessary supportive care and equipment is immediately available.
    b) Mild cases (urticaria only) may be treated with antihistamines, with or without epinephrine. Treatment of severe cases includes oxygen supplementation, aggressive airway management (may need intubation), epinephrine, EKG monitoring, and IV fluids (if hypotensive).
    4) Treatment should always be done on the advice and with the consultation of a veterinarian. Additional information regarding treatment of poisoned animals may be obtained from a Board Certified (ABVT) Veterinary Toxicologist (check with nearest veterinary school or veterinary diagnostic laboratory) or the National Animal Poison Control Center.
    5) ANIMAL POISON CONTROL CENTERS
    a) ASPCA Animal Poison Control Center, An Allied Agency of the University of Illinois, 1717 S. Philo Rd, Suite 36, Urbana, IL 61802, website www.aspca.org/apcc
    b) It is an emergency telephone service which provides toxicology information to veterinarians, animal owners, universities, extension personnel and poison center staff for a fee. A veterinary toxicologist is available for consultation.
    c) The following 24-hour phone number is available: (888) 426-4435. A fee may apply. Please inquire with the poison center. The agency will make follow-up calls as needed in critical cases at no extra charge.
    11.2.2) LIFE SUPPORT
    A) GENERAL
    1) MAINTAIN VITAL FUNCTIONS: Secure airway, supply oxygen, and begin supportive fluid therapy if necessary.
    11.2.5) TREATMENT
    A) GENERAL TREATMENT
    1) ANAPHYLAXIS -
    a) AIRWAY - Maintain a patent airway via endotracheal tube or tracheostomy.
    b) EPINEPHRINE - For severe reactions. DOGS: 0.5 to 1 milliliter of 1:10,000 (DILUTE) solution intravenously or subcutaneously; CATS: 0.5 ml of 1:10,000 (DILUTE) solution intravenously or intramuscularly. Be sure to dilute epinephrine from the bottle (1:1000) one part to 9 parts saline to obtain the correct concentration (1:10,000). If indicated, dose may be repeated in 20 minutes.
    c) FLUID THERAPY - If necessary, begin fluid therapy at maintenance doses (66 milliliters solution/kilogram body weight/day intravenously) or, in hypotensive patients, at high doses (up to shock dose 60 milliliters/kilogram/hour). Monitor for urine production and pulmonary edema.
    d) ANTIHISTAMINES/STEROIDS - Administer doxylamine succinate (1 to 2.2 milligram/kilogram subcutaneously or intramuscularly every 8 to 12 hours), dexamethasone sodium phosphate (1 to 5 milligram/kilogram intravenously every 12 to 24 hours), or prednisolone (1 to 5 milligram/kilogram intravenously every 1 to 6 hours).
    1) Diphenhydrinate may also be used in dogs and cats at a dose of 0.5 mg/kg IM/IV, followed by 2-4 mg/kg PO every 8 hours.
    2) LOCAL REACTIONS -
    a) Treat symptomatically. Permanent scarring may occur.
    b) Food animal carcasses or parts thereof may be condemned at slaughter.

Continuing Care

    11.4.1) SUMMARY
    11.4.1.2) DECONTAMINATION/TREATMENT
    A) GENERAL TREATMENT
    1) Begin treatment immediately.
    2) Remove the patient and other animals from the source of contamination.
    3) ANAPHYLAXIS -
    a) The use of any biological, such as vaccines, may cause an anaphylactoid reaction. Vaccines should not be administered outside of a medical environment unless the necessary supportive care and equipment is immediately available.
    b) Mild cases (urticaria only) may be treated with antihistamines, with or without epinephrine. Treatment of severe cases includes oxygen supplementation, aggressive airway management (may need intubation), epinephrine, EKG monitoring, and IV fluids (if hypotensive).
    4) Treatment should always be done on the advice and with the consultation of a veterinarian. Additional information regarding treatment of poisoned animals may be obtained from a Board Certified (ABVT) Veterinary Toxicologist (check with nearest veterinary school or veterinary diagnostic laboratory) or the National Animal Poison Control Center.
    5) ANIMAL POISON CONTROL CENTERS
    a) ASPCA Animal Poison Control Center, An Allied Agency of the University of Illinois, 1717 S. Philo Rd, Suite 36, Urbana, IL 61802, website www.aspca.org/apcc
    b) It is an emergency telephone service which provides toxicology information to veterinarians, animal owners, universities, extension personnel and poison center staff for a fee. A veterinary toxicologist is available for consultation.
    c) The following 24-hour phone number is available: (888) 426-4435. A fee may apply. Please inquire with the poison center. The agency will make follow-up calls as needed in critical cases at no extra charge.

Kinetics

    11.5.1) ABSORPTION
    A) GENERAL
    1) Animal kinetics vary depending on the preparation and the animal species involved.

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